GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P55040	P27348	binding	up-regulates quantity by stabilization	0.266	In order to address whether Gem binds specific isoforms of 14-3-3, we determined the coassociation of Gem and 14-3-3 in the neuroblastoma cell line SY5Y. 14-3-3ζ, -γ, -τ, and -β were observed to bind to Gem. 14-3-3-bound Gem has a twofold-longer half-life than nonbound Gem (Fig. (Fig.6).6). A similar increase in protein stability following 14-3-3 binding has been described for the Wee1 kinase	SIGNOR-261724
P11309	P17612	phosphorylation	up-regulates activity	0.266	In this study, we found that PKCα stabilized and activated PIM-1L by phosphorylation at Ser65. The PIM-1L phosphorylation suppressed sotrastaurin-induced apoptosis. These findings suggest that PKCα promotes cell survival and proliferation by upregulating PIM-1L in acute myeloid leukemia.	SIGNOR-256153
P46531	Q9UQF2	binding	down-regulates	0.266	Here, we show that jip1 suppresses notch1 activity. Jip1 was found to physically associate with either intracellular domain of notch1 or rbp-jk and interfere with the interaction between them.	SIGNOR-165710
O15054	Q16665	transcriptional regulation	up-regulates quantity by expression	0.266	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271571
Q7KZI7	Q05513	phosphorylation	down-regulates	0.266	Hpar-1b is phosphorylated by apkc on threonine 595 importantly, phosphorylation of hpar-1b on t595 negatively regulates the kinase activity and plasma membrane localization of hpar-1b in vivo.	SIGNOR-124217
P08047	P62136	dephosphorylation	down-regulates activity	0.266	Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.	SIGNOR-251952
Q16635	P06493	phosphorylation	down-regulates quantity by destabilization	0.266	Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.	SIGNOR-278240
P20339	Q99698	binding	down-regulates activity	0.266	Mauve interacts with Rab5, Msps, and gamma-tubulin\|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment	SIGNOR-266001
Q9UHD2	Q14289	phosphorylation	up-regulates activity	0.266	Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation.	SIGNOR-277910
P42773	Q13351	transcriptional regulation	up-regulates quantity by expression	0.266	Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c.	SIGNOR-266046
P04040	Q05655	phosphorylation	up-regulates activity	0.266	Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167.	SIGNOR-260904
O60341	Q9C0F0	binding	down-regulates activity	0.266	Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.	SIGNOR-266764
O14757	P62714	dephosphorylation	down-regulates activity	0.266	Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit\|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.	SIGNOR-248578
P60880	Q86UW7	binding	up-regulates activity	0.266	CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1	SIGNOR-264339
P41161	P63279	sumoylation	down-regulates	0.266	Here we show that erm interacts with the sumo-conjugating enzyme ubc9 and is modified by sumo. We further show that sumo modification of this ets transcription factor affects its ability to activate transcription.	SIGNOR-135850
P14635	P50539	transcriptional regulation	down-regulates quantity by repression	0.266	Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression \| Mxi1 inhibits the promoter activity of the cyclin B1 gene.	SIGNOR-266064
Q9C0J9	Q13363	binding	up-regulates	0.266	We identify the ctip and ctbp corepressors as novel components of the human rbp-jkappa/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. Functionally, ctip and ctbp augment sharp-mediated repression.	SIGNOR-141613
Q14005	P27361	phosphorylation	up-regulates	0.266	The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 in antigen receptor-, sdf1alpha- and il-2-activated t cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.	SIGNOR-121856
Q9BZE0	Q9UMX1	relocalization	down-regulates	0.266	Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms.	SIGNOR-142608
Q14469	Q9UM73	phosphorylation	up-regulates activity	0.266	NPM-ALK also directly phosphorylates HES1 protein.	SIGNOR-280181
P01215	P50458	transcriptional regulation	up-regulates quantity by expression	0.266	In Cos cells, LH-2 activated the a-subunit promoter approximately twofold	SIGNOR-266055
P15531	P06493	phosphorylation	up-regulates	0.266	Application of this approach to the discovery of cdk1-cyclin b substrates yielded identification of >70 substrates and phosphorylation sites. Many of these sites are known to be phosphorylated in vivo, but most of the proteins have not been characterized as cdk1-cyclin b substrates.	SIGNOR-160493
O14795	Q9UJD0	relocalization	up-regulates activity	0.266	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264384
Q12857	Q01664	binding	up-regulates activity	0.266	We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads.	SIGNOR-226586
Q9UQ26	A6NJZ7	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264367
P17275	Q9Y222	transcriptional regulation	up-regulates quantity by expression	0.265	Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.	SIGNOR-261585
P53396	P12931	phosphorylation	up-regulates activity	0.265	We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells.	SIGNOR-274107
P09471	Q9UKP6	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257252
P08047	O00141	phosphorylation	up-regulates activity	0.265	In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking related genes .\|In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking-related genes xref .	SIGNOR-279246
P35638	Q13131	phosphorylation	down-regulates activity	0.265	Here, we report that phosphorylation of CHOP at Ser30 by AMPKα1 triggers CHOP degradation resulting in reduced macrophage apoptosis and subsequent ameliorated plaque vulnerability in vivo.	SIGNOR-259864
P09471	Q15722	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256970
P99999	Q9Y243	phosphorylation	down-regulates activity	0.265	Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.	SIGNOR-277235
P05107	O60674	phosphorylation	up-regulates activity	0.265	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254738
P17096	Q03135	relocalization	up-regulates activity	0.265	CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.	SIGNOR-254428
Q9Y4C1	Q99814	transcriptional regulation	up-regulates quantity by expression	0.265	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271583
P29372	Q13315	phosphorylation	up-regulates activity	0.265	ATM phosphorylates MPG at serine 172 (XREF_FIG).\|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity.	SIGNOR-279004
P42229	P23470	dephosphorylation	up-regulates activity	0.265	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254730
P19438	P02533	binding	down-regulates activity	0.265	TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.	SIGNOR-251906
P40763	Q13627	phosphorylation	up-regulates activity	0.265	DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS.	SIGNOR-279992
P46937	O00506	phosphorylation	up-regulates activity	0.265	Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.\|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.	SIGNOR-278993
P49840	P51812	phosphorylation	down-regulates activity	0.265	P90-rsk and akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively.	SIGNOR-110827
P51812	P31749	phosphorylation	down-regulates activity	0.265	Akt interacts with and phosphorylates RSK2 at S19.	SIGNOR-277548
Q9UQL6	O94806	phosphorylation	up-regulates activity	0.265	Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].	SIGNOR-275926
P10645	P16220	transcriptional regulation	up-regulates quantity by expression	0.265	Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.	SIGNOR-254276
O60341	Q16665	transcriptional regulation	down-regulates quantity by repression	0.265	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271573
P10636-2	P41743	phosphorylation	down-regulates activity	0.265	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275446
P10636-2	P17252	phosphorylation	down-regulates activity	0.265	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275441
Q92908	P49840	phosphorylation	down-regulates quantity by destabilization	0.265	Through bioinformatics and cell-based experiments, we identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin	SIGNOR-253156
Q9NQW6	Q9UM11	binding	down-regulates quantity by destabilization	0.265	Ubiquitination of anillin required a destruction-box and was mediated by Cdh1, an activator of APC/C. Overexpression of Cdh1 reduced the levels of anillin, whereas inactivation of APC/C(Cdh1) increased the half-life of anillin.	SIGNOR-272654
Q13562	Q14938	transcriptional regulation	up-regulates quantity	0.265	For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)	SIGNOR-268904
P08754	Q9UKP6	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257164
P31431	Q6UXX9	binding	up-regulates	0.265	We show that rspo3 binds syndecan 4 (sdc4) and that together they activate wnt/pcp signaling.	SIGNOR-172719
O60341	P49841	phosphorylation	up-regulates activity	0.265	GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.\|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.	SIGNOR-278225
P14598	O60381	transcriptional regulation	down-regulates quantity by repression	0.265	Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene.	SIGNOR-261614
Q13422	P62140	dephosphorylation	up-regulates	0.265	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174862
Q92769	P29475	s-nitrosylation	down-regulates activity	0.265	we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation	SIGNOR-236919
P08754	P41595	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256886
Q86UR5	A6NJZ7	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264362
P63096	Q9UKP6	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257051
P01178	P16519	cleavage	down-regulates quantity	0.265	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270328
P51452	P29597	phosphorylation	up-regulates	0.265	Phosphorylation of vhr at tyr(138) was required for its phosphatase activity toward stat5. In addition, the src homology 2 domain of stat5 was required for the effective dephosphorylation of stat5 by vhr. The tyrosine kinase tyk2, which mediates the phosphorylation of stat5, was also responsible for the phosphorylation of vhr at tyr(138).	SIGNOR-157655
P49418	P28482	phosphorylation	down-regulates activity	0.265	Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2.	SIGNOR-126859
Q9UJD0	A6NNM3	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264374
O95837	P21728	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257391
P01106	Q99608	transcriptional regulation	up-regulates quantity by expression	0.265	Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly.	SIGNOR-253381
P00441	P19544	transcriptional regulation	up-regulates quantity by expression	0.265	The human copper-zinc superoxide dismutase gene (SOD1) proximal promoter is regulated by Sp1, Egr-1, and WT1 via non-canonical binding sites. Egr-1 and two splicing variants of the Egr-related protein WT1 were able to transactivate the SOD1 promoter in co-transfection experiments.	SIGNOR-253898
Q96Q27	P28482	phosphorylation	up-regulates activity	0.265	Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. \|Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.	SIGNOR-272240
P38405	P32239	binding	up-regulates activity	0.265	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256908
Q14005	P28482	phosphorylation	up-regulates	0.265	The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 . the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.	SIGNOR-121852
Q9UJD0	A6NJZ7	binding	down-regulates activity	0.265	SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.	SIGNOR-264372
P29375	Q99814	transcriptional regulation	up-regulates quantity by expression	0.265	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271580
Q96Q27	P27361	phosphorylation	up-regulates activity	0.265	Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. \|Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.	SIGNOR-272241
P05556	P23470	dephosphorylation	down-regulates activity	0.265	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254706
O75874	P98177	transcriptional regulation	up-regulates quantity by expression	0.264	We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.	SIGNOR-260102
Q14449	P49840	phosphorylation	down-regulates activity	0.264	Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor\| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.	SIGNOR-264871
P31948	P06493	phosphorylation	down-regulates activity	0.264	Inactivation and phosphorylation mimicking of potential phosphorylation sites in mSTI1 altered the nuclear translocation. Mimicking of phosphorylation at the mSTI1 CKII phosphorylation site (S189E) promoted nuclear localization of mSTI1-EGFP. Mimicking phosphorylation at the cdc2 kinase phosphorylation site (T198E) promoted cytoplasmic localization of mSTI1-EGFP at the G1/S-phase transition,whereas removal of this site (T198A) promoted the nuclear localization of mSTI1-EGFP under the same conditions.	SIGNOR-262729
Q8NG66	O14757	phosphorylation	up-regulates	0.264	We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273	SIGNOR-187863
P54646	Q13315	phosphorylation	up-regulates activity	0.264	ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2\|	SIGNOR-275488
Q969H0	Q14258	ubiquitination	down-regulates activity	0.264	This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.	SIGNOR-277457
O75928	Q15759	phosphorylation	up-regulates activity	0.264	The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles	SIGNOR-262947
P11413	O15294	glycosylation	up-regulates activity	0.264	O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth\|O-GlcNAcylation of G6PD activates enzyme activity\|G6PD is dynamically modified by O-GlcNAc at serine 84\|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.	SIGNOR-267582
P08047	P67775	dephosphorylation	up-regulates activity	0.264	These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription	SIGNOR-248223
Q9NZ72	P49841	phosphorylation	up-regulates activity	0.264	Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.\|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta	SIGNOR-264882
Q96J02	Q13315	phosphorylation	up-regulates activity	0.264	Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH.	SIGNOR-276488
Q12800	Q00526	phosphorylation	down-regulates	0.264	In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression	SIGNOR-184164
P17096	P24941	phosphorylation	down-regulates	0.264	Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.	SIGNOR-158612
P63092	P32239	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256765
Q07866	P27361	phosphorylation	down-regulates	0.264	Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.	SIGNOR-172642
Q92570	P04637	transcriptional regulation	up-regulates quantity by expression	0.264	We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.	SIGNOR-256200
P13639	P41240	phosphorylation	down-regulates quantity	0.264	C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.\|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus.	SIGNOR-279698
P56178	P31749	phosphorylation	up-regulates	0.264	Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5. akt interacts with and phosphorylates dlx5. In addition, we provide evidences that akt kinase activity is important for akt to enhance the protein stability and transcriptional activity of dlx5.	SIGNOR-252513
P25025	P37231	transcriptional regulation	up-regulates quantity by expression	0.264	EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE).	SIGNOR-271682
Q9UI33	P61328	binding	down-regulates activity	0.264	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253436
P38405	P32238	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256906
P56524	Q96GD4	phosphorylation	down-regulates	0.264	We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions	SIGNOR-198646
O95837	P21918	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257418
P62826	P53350	phosphorylation	up-regulates	0.264	Plk1 is capable of phosphorylating co-immunoprecipitated ran in vitro on serine-135 and ran is phosphorylated in vivo at the same site during mitosis when plk1 is normally activated. Deregulation of ran phosphorylation disrupts normal spindle structure and segregation of chromosomes.	SIGNOR-149073
Q05397	Q13882	phosphorylation	up-regulates activity	0.264	B. PTK6 phosphorylates FAK at tyrosine residue 861.\|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.	SIGNOR-278428
P63092	P32238	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256763
P08754	O43614	binding	up-regulates activity	0.264	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256872

P55040

P27348

0

binding

up-regulates quantity by stabilization

0.266

In order to address whether Gem binds specific isoforms of 14-3-3, we determined the coassociation of Gem and 14-3-3 in the neuroblastoma cell line SY5Y. 14-3-3ζ, -γ, -τ, and -β were observed to bind to Gem. 14-3-3-bound Gem has a twofold-longer half-life than nonbound Gem (Fig. (Fig.6).6). A similar increase in protein stability following 14-3-3 binding has been described for the Wee1 kinase

SIGNOR-261724

P11309

P17612

0

phosphorylation

up-regulates activity

0.266

In this study, we found that PKCα stabilized and activated PIM-1L by phosphorylation at Ser65. The PIM-1L phosphorylation suppressed sotrastaurin-induced apoptosis. These findings suggest that PKCα promotes cell survival and proliferation by upregulating PIM-1L in acute myeloid leukemia.

SIGNOR-256153

P46531

Q9UQF2

0

binding

down-regulates

0.266

Here, we show that jip1 suppresses notch1 activity. Jip1 was found to physically associate with either intracellular domain of notch1 or rbp-jk and interfere with the interaction between them.

SIGNOR-165710

O15054

Q16665

0

transcriptional regulation

up-regulates quantity by expression

0.266

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271571

Q7KZI7

Q05513

0

phosphorylation

down-regulates

0.266

Hpar-1b is phosphorylated by apkc on threonine 595 importantly, phosphorylation of hpar-1b on t595 negatively regulates the kinase activity and plasma membrane localization of hpar-1b in vivo.

SIGNOR-124217

P08047

P62136

0

dephosphorylation

down-regulates activity

0.266

Transcription factors Sp1 and Sp3 activate alpha-ENaC2 transcription through a GC-rich element (Sp1-binding site) in the promoter. Sp1 and Sp3 are essential for alpha-ENaC2 transcription in lung epithelial cells and that dephosphorylation of the Sp transcription factors by PP1 suppresses alpha-ENaC2 expression.

SIGNOR-251952

Q16635

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.266

Our studies suggest that phosphorylation and degradation of TAZ by Cdk1 may play important roles in apoptosis induced by antitubulin drugs.

SIGNOR-278240

P20339

Q99698

0

binding

down-regulates activity

0.266

Mauve interacts with Rab5, Msps, and gamma-tubulin|Mauve/LYST opposes Rab5, which promotes vesicle fusion affecting PCM recruitment

SIGNOR-266001

Q9UHD2

Q14289

0

phosphorylation

up-regulates activity

0.266

Mechanistically, we demonstrate that PTK2B directly phosphorylates residue Tyr591 of TBK1, which increases TBK1 oligomerization and activation.

SIGNOR-277910

P42773

Q13351

0

transcriptional regulation

up-regulates quantity by expression

0.266

Thus, EKLF is a direct regulator of p18INK4c gene expression, and much of EKLF's role in driving erythroid cell differentiation may occur via p18INK4c.

SIGNOR-266046

P04040

Q05655

0

phosphorylation

up-regulates activity

0.266

Endothelin-1 stimulates catalase activity through the PKCδ-mediated phosphorylation of serine 167.

SIGNOR-260904

O60341

Q9C0F0

0

binding

down-regulates activity

0.266

Here, we showed that ASXL3 interacts with HP1α and LSD1, leading to transcriptional repression.

SIGNOR-266764

O14757

P62714

0

dephosphorylation

down-regulates activity

0.266

Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit|In response to genotoxic stress, Chk1 is phosphorylated on serines 317 (S317) and 345 (S345) by the ataxia-telangiectasia-related (ATR) protein kinase. Phosphorylation of Chk1 on these C-terminal serine residues is used as an indicator of Chk1 activation in vivo.

SIGNOR-248578

P60880

Q86UW7

0

binding

up-regulates activity

0.266

CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1

SIGNOR-264339

P41161

P63279

0

sumoylation

down-regulates

0.266

Here we show that erm interacts with the sumo-conjugating enzyme ubc9 and is modified by sumo. We further show that sumo modification of this ets transcription factor affects its ability to activate transcription.

SIGNOR-135850

P14635

P50539

0

transcriptional regulation

down-regulates quantity by repression

0.266

Mxi1 inhibits the proliferation of U87 glioma cells through down-regulation of cyclin B1 gene expression | Mxi1 inhibits the promoter activity of the cyclin B1 gene.

SIGNOR-266064

Q9C0J9

Q13363

0

binding

up-regulates

0.266

We identify the ctip and ctbp corepressors as novel components of the human rbp-jkappa/sharp-corepressor complex and show that ctip binds directly to the sharp repression domain. Functionally, ctip and ctbp augment sharp-mediated repression.

SIGNOR-141613

Q14005

P27361

0

phosphorylation

up-regulates

0.266

The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 in antigen receptor-, sdf1alpha- and il-2-activated t cells. Genetic and pharmacological-inhibitor experiments showed that the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.

SIGNOR-121856

Q9BZE0

Q9UMX1

0

relocalization

down-regulates

0.266

Negative regulation of gli1 and gli2 activator function by suppressor of fused through multiple mechanisms.Together, these observations reveal that su(fu) regulates the activity of gli1 and gli2 through distinct cytoplasmic and nuclear mechanisms.

SIGNOR-142608

Q14469

Q9UM73

0

phosphorylation

up-regulates activity

0.266

NPM-ALK also directly phosphorylates HES1 protein.

SIGNOR-280181

P01215

P50458

0

transcriptional regulation

up-regulates quantity by expression

0.266

In Cos cells, LH-2 activated the a-subunit promoter approximately twofold

SIGNOR-266055

P15531

P06493

0

phosphorylation

up-regulates

0.266

Application of this approach to the discovery of cdk1-cyclin b substrates yielded identification of >70 substrates and phosphorylation sites. Many of these sites are known to be phosphorylated in vivo, but most of the proteins have not been characterized as cdk1-cyclin b substrates.

SIGNOR-160493

O14795

Q9UJD0

0

relocalization

up-regulates activity

0.266

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264384

Q12857

Q01664

0

binding

up-regulates activity

0.266

We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads.

SIGNOR-226586

Q9UQ26

A6NJZ7

0

binding

down-regulates activity

0.265

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264367

P17275

Q9Y222

0

transcriptional regulation

up-regulates quantity by expression

0.265

Notably, amphiregulin (Areg), thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null mice while Gas1 and Ect2 genes were upregulated.

SIGNOR-261585

P53396

P12931

0

phosphorylation

up-regulates activity

0.265

We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells.

SIGNOR-274107

P09471

Q9UKP6

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257252

P08047

O00141

0

phosphorylation

up-regulates activity

0.265

In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking related genes .|In fact, SGK1 activates and phosphorylates SP1 on serine 59, a regulator of nucleocytoplasmic trafficking-related genes xref .

SIGNOR-279246

P35638

Q13131

0

phosphorylation

down-regulates activity

0.265

Here, we report that phosphorylation of CHOP at Ser30 by AMPKα1 triggers CHOP degradation resulting in reduced macrophage apoptosis and subsequent ameliorated plaque vulnerability in vivo.

SIGNOR-259864

P09471

Q15722

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256970

P99999

Q9Y243

0

phosphorylation

down-regulates activity

0.265

Finally, we propose that pro-survival kinase Akt (protein kinase B) is a likely mediator of the S47 phosphorylation of Cytc in the brain.

SIGNOR-277235

P05107

O60674

0

phosphorylation

up-regulates activity

0.265

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254738

P17096

Q03135

0

relocalization

up-regulates activity

0.265

CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization.

SIGNOR-254428

Q9Y4C1

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.265

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271583

P29372

Q13315

0

phosphorylation

up-regulates activity

0.265

ATM phosphorylates MPG at serine 172 (XREF_FIG).|In summary, our results show that ATM and MPG are directly associated in vitro and in vivo, phosphorylation of MPG at serine 172 is dependent on ATM and that of loss of phospho ATM reduces MPG glycosylase activity.

SIGNOR-279004

P42229

P23470

0

dephosphorylation

up-regulates activity

0.265

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254730

P19438

P02533

0

binding

down-regulates activity

0.265

TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.

SIGNOR-251906

P40763

Q13627

0

phosphorylation

up-regulates activity

0.265

DYRK1A overexpression promotes STAT3 activity by phosphorylating STAT3 at Ser727 and contributes to reduced neuronal production and increased astroglial generation in DS.

SIGNOR-279992

P46937

O00506

0

phosphorylation

up-regulates activity

0.265

Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results.

SIGNOR-278993

P49840

P51812

0

phosphorylation

down-regulates activity

0.265

P90-rsk and akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively.

SIGNOR-110827

P51812

P31749

0

phosphorylation

down-regulates activity

0.265

Akt interacts with and phosphorylates RSK2 at S19.

SIGNOR-277548

Q9UQL6

O94806

0

phosphorylation

up-regulates activity

0.265

Histone deacetylase (HDAC) 5 and 7, two members of the class II of classical HDAC [62], are in vivo substrates of PKD3 and PKD [63]. In response to a variety of signals, including phorbol esters, T cell receptor engagement, vascular endothelial growth factor and angiotensin stimulation, the activity of HDAC5 and 7 are regulated by a mechanism that involves PKD3 and PKD-mediated phosphorylation of the highly conserved Ser259 and Ser498 residues that are located in N-terminus of class II HDACs [63–67].

SIGNOR-275926

P10645

P16220

0

transcriptional regulation

up-regulates quantity by expression

0.265

Recently, binding of specific protein 1 (Sp1) and cAMP response element binding protein (CREB) to a GC-rich element at -92/-62 has been identified as a critical step in gastrin-dependent regulation of the chromogranin A (CgA) gene in gastric epithelial cells. Here we demonstrate that binding of early growth response protein 1 (Egr-1) to the distal part of the -92/-62 site is also required for gastrin-dependent CgA transactivation.

SIGNOR-254276

O60341

Q16665

0

transcriptional regulation

down-regulates quantity by repression

0.265

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271573

P10636-2

P41743

0

phosphorylation

down-regulates activity

0.265

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275446

P10636-2

P17252

0

phosphorylation

down-regulates activity

0.265

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275441

Q92908

P49840

0

phosphorylation

down-regulates quantity by destabilization

0.265

Through bioinformatics and cell-based experiments, we identified the AKT-repressed signal as glycogen synthase kinase 3 (GSK3)-catalyzed phosphorylation of Ser(37) on the long form of the transcription factor GATA6. Phosphorylation of GATA6 on Ser(37) promoted its degradation, thereby preventing GATA6 from repressing transcripts that are induced by TNF and attenuated by insulin

SIGNOR-253156

Q9NQW6

Q9UM11

0

binding

down-regulates quantity by destabilization

0.265

Ubiquitination of anillin required a destruction-box and was mediated by Cdh1, an activator of APC/C. Overexpression of Cdh1 reduced the levels of anillin, whereas inactivation of APC/C(Cdh1) increased the half-life of anillin.

SIGNOR-272654

Q13562

Q14938

0

transcriptional regulation

up-regulates quantity

0.265

For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)

SIGNOR-268904

P08754

Q9UKP6

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257164

P31431

Q6UXX9

0

binding

up-regulates

0.265

We show that rspo3 binds syndecan 4 (sdc4) and that together they activate wnt/pcp signaling.

SIGNOR-172719

O60341

P49841

0

phosphorylation

up-regulates activity

0.265

GSK3beta phosphorylates KDM1A serine 683 upon priming phosphorylation of KDM1A serine 687 by CK1alpha.|Together, these results support the notion that GSK3\u03b2 stabilizes KDM1A by decreasing its ubiquitination.

SIGNOR-278225

P14598

O60381

0

transcriptional regulation

down-regulates quantity by repression

0.265

Together, these results indicate that HBP1 may contribute to the regulation of NADPH oxidase-dependent superoxide production through transcriptional repression of the p47phox gene.

SIGNOR-261614

Q13422

P62140

0

dephosphorylation

up-regulates

0.265

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174862

Q92769

P29475

0

s-nitrosylation

down-regulates activity

0.265

we found that restoration of NO signaling in vivo, by adenoviral-mediated expression of a constitutively active endothelial NOS mutant in MDX muscles, and in vitro, by exposing MDX-derived satellite cells to NO donors, resulted in HDAC2 blockade by cysteine S-nitrosylation

SIGNOR-236919

P08754

P41595

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256886

Q86UR5

A6NJZ7

0

binding

down-regulates activity

0.265

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264362

P63096

Q9UKP6

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257051

P01178

P16519

0

cleavage

down-regulates quantity

0.265

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270328

P51452

P29597

0

phosphorylation

up-regulates

0.265

Phosphorylation of vhr at tyr(138) was required for its phosphatase activity toward stat5. In addition, the src homology 2 domain of stat5 was required for the effective dephosphorylation of stat5 by vhr. The tyrosine kinase tyk2, which mediates the phosphorylation of stat5, was also responsible for the phosphorylation of vhr at tyr(138).

SIGNOR-157655

P49418

P28482

0

phosphorylation

down-regulates activity

0.265

Thus, we propose that mapk phosphorylation of amphiphysin1 controls ngf receptor/trka-mediated endocytosis by terminating the amphiphysin1-ap-2 interaction.Our results indicate that phosphorylation of amphiphysin 1 at ser-285 and/or ser-293 affects the function of amphiphysin1.Mapk phosphorylation of ser-285 and ser-293 could modulate the interaction between prd and ap-2, resulting in the dissociation of amphiphysin1 from ap-2.

SIGNOR-126859

Q9UJD0

A6NNM3

0

binding

down-regulates activity

0.265

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264374

O95837

P21728

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257391

P01106

Q99608

0

transcriptional regulation

up-regulates quantity by expression

0.265

Deletion mapping demonstrated that the C-terminus of cystin and both termini of necdin are required for their mutual interaction. Speculating that these two proteins may function to regulate gene expression, we developed a luciferase reporter assay and observed that necdin strongly activated the Myc P1 promoter, and cystin did so more modestly.

SIGNOR-253381

P00441

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.265

The human copper-zinc superoxide dismutase gene (SOD1) proximal promoter is regulated by Sp1, Egr-1, and WT1 via non-canonical binding sites. Egr-1 and two splicing variants of the Egr-related protein WT1 were able to transactivate the SOD1 promoter in co-transfection experiments.

SIGNOR-253898

Q96Q27

P28482

0

phosphorylation

up-regulates activity

0.265

Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.

SIGNOR-272240

P38405

P32239

0

binding

up-regulates activity

0.265

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256908

Q14005

P28482

0

phosphorylation

up-regulates

0.265

The precursor form of the cytokine il-16 (proil-16) was shown to be phosphorylated on ser144 . the phosphorylation of proil-16 is dependent on activation of the kinases erk1/2. Il-16 is secreted by mitogen-activated t cells, and the biochemical link between proil-16 and erk1/2, revealed by studies with pap-1, prompted analysis of the role of map kinases in this response.

SIGNOR-121852

Q9UJD0

A6NJZ7

0

binding

down-regulates activity

0.265

SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.

SIGNOR-264372

P29375

Q99814

0

transcriptional regulation

up-regulates quantity by expression

0.265

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271580

Q96Q27

P27361

0

phosphorylation

up-regulates activity

0.265

Indeed, using mass spectrometry, we showed for the first time that ASB2a is phosphorylated and that phosphorylation of serine-323 (Ser-323) of ASB2a is crucial for the targeting of the actin-binding protein filamin A (FLNa) to degradation. |Moreover, inhibition of the extracellular signal-regulated kinases 1 and 2 (Erk1/2) activity reduced ASB2a-mediated FLNa degradation.

SIGNOR-272241

P05556

P23470

0

dephosphorylation

down-regulates activity

0.265

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254706

O75874

P98177

0

transcriptional regulation

up-regulates quantity by expression

0.264

We identify FOXOs as transcriptional activators of IDH1. FOXOs promote IDH1 expression and thereby maintain the cytosolic levels of α-ketoglutarate and NADPH.

SIGNOR-260102

Q14449

P49840

0

phosphorylation

down-regulates activity

0.264

Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.

SIGNOR-264871

P31948

P06493

0

phosphorylation

down-regulates activity

0.264

Inactivation and phosphorylation mimicking of potential phosphorylation sites in mSTI1 altered the nuclear translocation. Mimicking of phosphorylation at the mSTI1 CKII phosphorylation site (S189E) promoted nuclear localization of mSTI1-EGFP. Mimicking phosphorylation at the cdc2 kinase phosphorylation site (T198E) promoted cytoplasmic localization of mSTI1-EGFP at the G1/S-phase transition,whereas removal of this site (T198A) promoted the nuclear localization of mSTI1-EGFP under the same conditions.

SIGNOR-262729

Q8NG66

O14757

0

phosphorylation

up-regulates

0.264

We demonstrate that chk1 (checkpoint kinase 1) directly activates nek11 by phosphorylating it on ser 273

SIGNOR-187863

P54646

Q13315

0

phosphorylation

up-regulates activity

0.264

ATM phosphorylates AMPKalpha2 to induce inhibitory phosphorylation of HIPK2|

SIGNOR-275488

Q969H0

Q14258

0

ubiquitination

down-regulates activity

0.264

This newly stabilized TRIM25 then directly ubiquitinates Lys412 of FBXW7α, a core subunit of the SKP1-Cullin-F-box (SCF) ubiquitin ligase complex involved in Myc ubiquitination, thereby stabilizing Myc.

SIGNOR-277457

O75928

Q15759

0

phosphorylation

up-regulates activity

0.264

The switch between the coactivating and inhibitory actions of PIASxα is controlled, at least in part, through PIASxα phosphorylation. PIASxα is itself phosphorylated by p38 in vitro and in vivo in response to the activation of stress signaling pathways (Figure 2, Figure 3, Figure 4). We identify Ser113 and Ser 116 as two residues that are phosphorylated by p38 and have important functional roles

SIGNOR-262947

P11413

O15294

0

glycosylation

up-regulates activity

0.264

O-GlcNAcylation of G6PD promotes the pentose phosphate pathway and tumor growth|O-GlcNAcylation of G6PD activates enzyme activity|G6PD is dynamically modified by O-GlcNAc at serine 84|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.

SIGNOR-267582

P08047

P67775

0

dephosphorylation

up-regulates activity

0.264

These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription

SIGNOR-248223

Q9NZ72

P49841

0

phosphorylation

up-regulates activity

0.264

Altogether, these results indicate that CDK5 phosphorylates similarly serines 68 and 73, whereas ERK2 targets mostly serine 68 and GSK-3beta mostly serine 60.|This observation may support the hypothesis of a specific localization of stathmin 3 depending on its phosphorylation by GSK-3beta

SIGNOR-264882

Q96J02

Q13315

0

phosphorylation

up-regulates activity

0.264

Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH.

SIGNOR-276488

Q12800

Q00526

0

phosphorylation

down-regulates

0.264

In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression

SIGNOR-184164

P17096

P24941

0

phosphorylation

down-regulates

0.264

Here, we found that hipk2 phosphorylates hmga1a at ser-35, thr-52, and thr-77, and hmga1b at thr-41 and thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate hmga1 proteins, could induce the phosphorylation of hmga1 proteins at the same ser/thr sites. we found that the hipk2-phosphorylated hmga1a reduced the binding affinity of hmga1a to human germ line promoter, and the drop in binding affinity induced by hipk2 phosphorylation was lower than that introduced by cdc2 phosphorylation.

SIGNOR-158612

P63092

P32239

0

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256765

Q07866

P27361

0

phosphorylation

down-regulates

0.264

Phosphorylation of kinesin light chain 1 at serine 460 modulates binding and trafficking of calsyntenin-1mutation of klc1ser460 to an alanine residue, to preclude phosphorylation, increased the binding of calsyntenin-1, whereas mutation to an aspartate residueklc1ser460 is a predicted mitogen-activated protein kinase (mapk) target site, and we show that extracellular-signal-regulated kinase (erk) phosphorylates this residue in vitro.

SIGNOR-172642

Q92570

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.264

We showed that p53 directly bound the promoter of NR4A3 gene and induced its transcription. p53 transactivates the NR4A3 promoter in H1299 cells.

SIGNOR-256200

P13639

P41240

0

phosphorylation

down-regulates quantity

0.264

C-terminal Src kinase (Csk)-mediated phosphorylation of eukaryotic elongation factor 2 (eEF2) promotes proteolytic cleavage and nuclear translocation of eEF2.|In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus.

SIGNOR-279698

P56178

P31749

0

phosphorylation

up-regulates

0.264

Akt, a member of the ser-ine/threonine-specific protein kinase, was found to phosphorylate osx and dlx5. akt interacts with and phosphorylates dlx5. In addition, we provide evidences that akt kinase activity is important for akt to enhance the protein stability and transcriptional activity of dlx5.

SIGNOR-252513

P25025

P37231

0

transcriptional regulation

up-regulates quantity by expression

0.264

EMSA, ChIP, and transient transfection assays indicate that PPAR-gamma activates the CXCR2 promoter by binding to a PPAR response element (PPRE).

SIGNOR-271682

Q9UI33

P61328

0

binding

down-regulates activity

0.264

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253436

P38405

P32238

0

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256906

P56524

Q96GD4

0

phosphorylation

down-regulates

0.264

We define the precise site of aurb-mediated phosphorylation as a conserved serine within the nuclear localization signals of hdac4, hdac5, and hdac9 at ser265, ser278, and ser242, respectivelyduring mitosis, aurb-mediated phosphorylation may localize class iia hdacs to a phosphorylation gradient at the spindle midzone, permitting temporal and spatial regulatory mechanisms altering hdac protein interactions

SIGNOR-198646

O95837

P21918

0

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257418

P62826

P53350

0

phosphorylation

up-regulates

0.264

Plk1 is capable of phosphorylating co-immunoprecipitated ran in vitro on serine-135 and ran is phosphorylated in vivo at the same site during mitosis when plk1 is normally activated. Deregulation of ran phosphorylation disrupts normal spindle structure and segregation of chromosomes.

SIGNOR-149073

Q05397

Q13882

0

phosphorylation

up-regulates activity

0.264

B. PTK6 phosphorylates FAK at tyrosine residue 861.|Knockdown of PTK6 in the PC3 human prostate cancer cell line disrupts FAK and AKT activation and promotes anoikis, which can be rescued by exogenous expression of FAK.

SIGNOR-278428

P63092

P32238

0

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256763

P08754

O43614

0

binding

up-regulates activity

0.264

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256872