GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P05129	Q92686	1	phosphorylation	up-regulates activity	0.429	Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.	SIGNOR-248915
Q13882	P51692	1	phosphorylation	up-regulates	0.429	Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.	SIGNOR-159066
Q13627	O95644	1	phosphorylation	up-regulates activity	0.429	DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.\|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.	SIGNOR-278278
Q99835	P08754	1	binding	up-regulates	0.429	Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.	SIGNOR-199165
P24941	P12830	1	phosphorylation	down-regulates quantity by destabilization	0.429	Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP	SIGNOR-274049
Q13315	P53350	1	phosphorylation	down-regulates activity	0.429	Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5\u20137,18] , whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5\u201319] .\|Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5-7,18], whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5-19].	SIGNOR-279793
P16234	Q05397	1	phosphorylation	up-regulates activity	0.429	Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met.	SIGNOR-259400
P04637	O15527	1	transcriptional regulation	up-regulates quantity by expression	0.429	Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1.	SIGNOR-255440
Q13287	P56693	1	binding	up-regulates activity	0.429	we identify an association of Sox10 with the N-myc interactor Nmi. Nmi modulated the transcriptional activity of Sox10 in reporter gene assays. Nmi effects varied between different Sox10 target gene promoters, indicating that Nmi function in vivo may be promoter-specific.	SIGNOR-225599
P17612	P48058	1	phosphorylation	up-regulates	0.429	We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus.	SIGNOR-97550
P24941	Q9Y618	1	phosphorylation	down-regulates activity	0.429	Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT.\|Cdk2 phosphorylates SMRT at consensus Cdk motifs to generate Pin1 binding sites and consequently targets SMRT for degradation, the latter also requiring the PPIase activity of Pin1 (XREF_FIG).	SIGNOR-278306
O15111	P04637	1	phosphorylation	up-regulates activity	0.429	In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.\|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].	SIGNOR-280231
Q5VTB9	O75182	1	polyubiquitination	down-regulates quantity by destabilization	0.429	Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B.	SIGNOR-271943
Q15759	O60381	1	phosphorylation	up-regulates	0.428	A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression.	SIGNOR-119134
P61088	Q12933	2	ubiquitination	up-regulates activity	0.428	Intact ring and zinc finger domains are required for tnfalfa-induced traf2 ubiquitination, which is also dependent on ubc13. Traf2 ubiquitination coincides with its translocation to the insoluble cellular fraction, resulting in selective activation of jnk. Ubc13 expression by rnai resulted in tnfalfa-induced traf2 translocation and impaired activation of jnk but not of ikk or p38.	SIGNOR-121274
P51608	Q8NFU7	1	binding	up-regulates activity	0.428	MeCP2 and its partners, splicing factor Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to BDNF chromatin in naı ̈ve but dissociate during conditioning\|Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and CTCF binding thereby negatively impacting DNA methylation and conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have secondary effects on DNA methylation and alternative splicing.	SIGNOR-277701
P36897	Q9Y4K3	1	binding	up-regulates activity	0.428	We report here that TRAF6 is specifically required for the Smad-independent activation of JNK and p38 and its carboxyl TRAF homology domain physically interacts with TGF-² receptors	SIGNOR-241918
P49841	Q14596	1	phosphorylation	down-regulates activity	0.428	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261795
Q12933	P61088	2	binding	up-regulates activity	0.428	Traf2, ubc13, and ikkgamma were required for complex assembly and activation of mekk1 and mapk cascades.	SIGNOR-179479
P35367	P50148	1	binding	up-regulates activity	0.428	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-257376
Q9ULU8	P63027	1	binding	up-regulates activity	0.428	CAPS interactions with N-terminal regions of the SNARE motif of VAMP2 were also detected, which suggests that CAPS might recruit VAMP2 into syntaxin-1/SNAP-25 heterodimers for RQaQbc-SNARE complex assembly.	SIGNOR-264340
Q13555	Q9UQL6	1	phosphorylation	down-regulates	0.428	Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.	SIGNOR-85102
P45983	O95140	1	phosphorylation	down-regulates quantity	0.428	We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.	SIGNOR-274138
P42224	P35228	1	transcriptional regulation	up-regulates quantity by expression	0.428	STAT1 binds as a homodimer to cis elements known as gammaactivated sequences in the promoters of the genes encoding NOS2, the MHC class II transactivator (CIITA) and IL-12, among others.	SIGNOR-249497
Q16828	Q12778	1	dephosphorylation	up-regulates activity	0.428	It has been previously demonstrated that MKP-3 dephosphorylates FOXO1 on Ser256 and promotes nuclear translocation of FOXO1 , which subsequentially binds to the promoters of gluconeogenic genes and turns on the gluconeogenic program.\|We also reported that MKP-3 can activate FOXO1 by at least dephosphorylating Ser 256, one of the Akt phosphorylation sites xref .	SIGNOR-276983
Q12778	P35558	1	transcriptional regulation	up-regulates quantity by expression	0.428	Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase).	SIGNOR-197200
Q9BQ95	Q7Z434	1	binding	up-regulates activity	0.428	ECSIT interacts with IPS-1\|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation	SIGNOR-260371
Q14289	P40763	1	phosphorylation	up-regulates activity	0.428	These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.\|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).	SIGNOR-279429
P52333	Q15910	1	phosphorylation	up-regulates activity	0.428	These results demonstrate that phosphorylation of EZH2 by JAK3 on the Y244 increases the interaction with Polymerase II and decreases the association with PRC2 components promoting the expression of non-canonical genes.\|To explore the mechanism of JAK3 mediated EZH2 activation, the authors performed co-immunoprecipitation assays, which revealed interaction of EZH2 with JAK3 and polymerase II.	SIGNOR-278518
Q8TD08	P05412	1	phosphorylation	up-regulates	0.428	Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation.	SIGNOR-91375
O60566	P25054	1	phosphorylation	up-regulates activity	0.428	These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.\|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.	SIGNOR-279393
Q8TAU0	Q13477	1	transcriptional regulation	up-regulates quantity by expression	0.428	We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly	SIGNOR-266219
P00558	Q15118	1	phosphorylation	up-regulates activity	0.428	Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex.	SIGNOR-278365
P27361	P10828	1	phosphorylation	down-regulates activity	0.428	We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.	SIGNOR-102224
P31749	Q16875	1	phosphorylation	up-regulates	0.427	We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.	SIGNOR-252477
P53350	O95271	1	phosphorylation	up-regulates quantity by stabilization	0.427	Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends.	SIGNOR-276245
Q13627	P10636	1	phosphorylation	down-regulates	0.427	Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna	SIGNOR-171030
Q15759	P05787	1	phosphorylation	up-regulates	0.427	Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.	SIGNOR-114063
Q8NEZ5	P35613	1	ubiquitination	down-regulates quantity by destabilization	0.427	F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells	SIGNOR-273452
Q9UQM7	P14136	1	phosphorylation	down-regulates activity	0.427	On the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did induce disassembly of the filament. Sequential analysis of the purified phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2 kinase, whereas Ser13, Ser17, Ser34, and Ser389 on GFAP were phosphorylated by Ca(2+)-CaM-dependent protein kinase II.	SIGNOR-250626
Q96EP1	P09874	1	polyubiquitination	down-regulates quantity by destabilization	0.427	Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.	SIGNOR-271470
Q99523	P02649	1	binding	up-regulates quantity	0.427	Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/Aβ complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of Aβ in the brain and in aggravated plaque burden. Sortilin interacts with all human APOE isoforms.	SIGNOR-273721
Q13043	P98177	1	phosphorylation	up-regulates	0.427	The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1	SIGNOR-178193
Q92834	P61006	1	guanine nucleotide exchange factor	up-regulates activity	0.427	PGR interacts with the small GTPase RAB8A, which participates in cilia biogenesis and maintenance. We show that RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange. RPGR functions as a GEF for RAB8A and RPGR–RAB8A association may facilitate ciliary trafficking.	SIGNOR-253030
P20749	Q13547	1	binding	up-regulates	0.427	We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, -3, and -6	SIGNOR-129801
O43426	Q12965	1	binding	up-regulates activity	0.427	We describe binding of two PRD-containing endocytic proteins, dynamin and synaptojanin-1, to the SH3 domain of Myo1E. This interaction was detected both in vitro, using pull-downs of purified proteins, and in vivo, using immunoprecipitation of protein complexes from synapse-enriched brain extract and immunolocalization of Myo1E and dynamin. Our observation of the interaction between human Myo1E and endocytic proteins suggests that this longtailed myosin may play a role in clathrin-dependent endocytosis.Interaction between Myo1E SH3 domain and PRD-containing endocytic proteins may promote recruitment of Myo1E to clathrin-coated structures since an inactivating mutation in the SH3 domain reduced Myo1E localization to clathrin-containing puncta.	SIGNOR-265423
Q8N9B8	P01116	1	guanine nucleotide exchange factor	up-regulates	0.427	Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.	SIGNOR-183826
Q5H9F3	P56524	1	binding	up-regulates activity	0.427	BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.	SIGNOR-259112
P85298	P61586	1	gtpase-activating protein	down-regulates activity	0.427	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260463
P68400	Q8IVP5	1	phosphorylation	down-regulates activity	0.427	Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.	SIGNOR-273622
Q99728	P03372	1	ubiquitination	down-regulates quantity	0.427	As shown in xref , both FOXK2 and BARD1 enhanced the ubiquitination of ER\u03b1, with the extent of ubiquitination being enhanced when both FOXK2 and BARD1 were overexpressed.\|These findings suggested that FOXK2 might act as a negative regulator of Estrogen receptor\u03b1, and its association with both Estrogen receptor\u03b1 and BRCA1/BARD1 could lead to the down-regulation of Estrogen receptor\u03b1 transcriptional activity, effectively regulating the function of Estrogen receptor\u03b1.	SIGNOR-278803
P07237	O75460	1	binding	down-regulates activity	0.427	The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.	SIGNOR-275573
P36956	Q8NBP7	1	transcriptional regulation	up-regulates quantity by expression	0.427	Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9.	SIGNOR-255222
P23760	Q9UJU2	1	binding	up-regulates activity	0.427	Pax3 binds to lef1 pax3 activity may directly effect the expression of factors regulated by signal transduction pathways dependent on lef1.	SIGNOR-162100
Q07912	P31749	1	phosphorylation	up-regulates activity	0.427	Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.	SIGNOR-252446
P45983	P31749	1	phosphorylation	up-regulates activity	0.427	We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase.	SIGNOR-252426
P67775	P23396	1	dephosphorylation	down-regulates	0.427	We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment.	SIGNOR-137963
P62136	P31749	1	dephosphorylation	down-regulates activity	0.426	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252603
O60885	Q09472	1	binding	up-regulates activity	0.426	In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. \|Together, these studies suggest that Brd4 enhances p300-mediated histone acetylation.	SIGNOR-262064
P27361	Q9UBN7	1	phosphorylation	up-regulates	0.426	Histone deacetylase 6 (hdac6) is well known for its ability to promote cell migrationextracellular signal-regulated kinase (erk) phosphorylates histone deacetylase 6 (hdac6) at serine 1035 to stimulate cell migrationwe have identified two novel erk-mediated phosphorylation sites: threonine 1031 and serine 1035 in hdac6. Both sites were phosphorylated by erk1	SIGNOR-202702
Q8IXJ6	P35558	1	deacetylation	up-regulates quantity by stabilization	0.426	Conversely, SIRT2 deacetylates and stabilizes PEPCK1.\|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1	SIGNOR-267599
Q9ULB1	Q14118	1	binding	up-regulates activity	0.426	The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.	SIGNOR-265458
P58400	Q14118	1	binding	up-regulates activity	0.426	The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.	SIGNOR-265459
P24941	P29374	1	phosphorylation	down-regulates	0.426	In the present study we identified rbp1 as a novel cdk substrate. Rbp1 is phosphorylated by cdk2 on serines 864 and 1007, which are n- and c-terminal to the lxcxe motif, respectively. Cdk2-mediated phosphorylation of rbp1 or prb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation	SIGNOR-170455
P47900	P30679	1	binding	up-regulates activity	0.426	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-257339
P31751	P15336	1	phosphorylation	up-regulates activity	0.426	Taken together, these data suggest that AMPK regulates EC migration through phosphorylation of AKT2, which promotes ATF2 transactivation of MMP-2 during EC migration.\|Within this subgroup, we chose AKT2 for analysis because AKT2 phosphorylates activating transcription factor 2 (ATF2) [ xref , xref ].	SIGNOR-280178
Q16539	P24385	1	phosphorylation	up-regulates	0.426	A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins	SIGNOR-166594
Q16236	P04040	1	transcriptional regulation	up-regulates quantity by expression	0.426	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254651
Q99684	P14921	2	binding	down-regulates activity	0.426	Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.	SIGNOR-254201
Q13546	Q5VWQ8	1	phosphorylation	up-regulates activity	0.426	We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC.	SIGNOR-259976
P46531	P15923	1	binding	down-regulates	0.426	We provide evidence that notch and deltex may act on e47 by inhibiting signaling through ras because (i) full e47 activity was found to be dependent on ras and (ii) both notch and deltex inhibited gal4-jun, a hybrid transcription factor whose activity is dependent on signaling from ras to sapk/jnk.	SIGNOR-56150
P10586	P07949	1	dephosphorylation	down-regulates	0.426	Lar expression significantly reduced tyrosine-1062 phosphorylation in ret-men2a but not in ret-men2b	SIGNOR-85170
P12931	P13688	1	phosphorylation	up-regulates activity	0.426	Recent reports have also suggested that Bgp1 behaves as a signal transduction molecule. Several physiological events promote the Tyr phosphorylation of Bgp1 on one or two Tyr residues within its cytoplasmic domain (Tyr-488 and Tyr-515). BGP becomes Tyr-phosphorylated by Src-like Tyr kinases in activated neutrophils (24) and in human colon carcinoma cellsWe have recently shown that Tyr phosphorylation of the mouse Bgp1 cytoplasmic domain in CT51 mouse colonic carcinoma cells led to its binding to the protein-Tyr phosphatase SHP-1 and that this event required the presence of both Tyr-488 and Tyr-515	SIGNOR-246471
P14921	Q99684	2	binding	down-regulates activity	0.426	Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.	SIGNOR-254202
P30411	P30679	1	binding	up-regulates activity	0.426	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-257281
P18847	Q99988	1	transcriptional regulation	up-regulates quantity by expression	0.426	In addition, DIM increased the expression of NAG-1 as well as activating transcription factor 3 (ATF3), and the induction of ATF3 was earlier than that of NAG-1. The DIM treatment increased luciferase activity of NAG-1 in HCT-116 cells transfected with NAG-1 promoter construct. The results suggest that I3C represses cell proliferation through up-regulation of NAG-1 and that ATF3 may play a pivotal role in DIM-induced NAG-1 expression in human colorectal cancer cells.	SIGNOR-253725
O14578	Q9NQS7	1	phosphorylation	up-regulates activity	0.426	Figure 5.CIT-K phosphorylates INCENP. (a) Schematic diagram of INCENP structure illustrating the phosphorylated sites identified by MS.	SIGNOR-280232
Q13418	Q13765	1	phosphorylation	up-regulates	0.426	Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.	SIGNOR-127694
Q13418	E9PAV3	1	phosphorylation	up-regulates	0.426	The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription	SIGNOR-127631
P00533	O15455	1	phosphorylation	up-regulates activity	0.426	Although both the ErbB1 and the ErbB2 isoforms of EGFR can bind to activated TLR3, functionally, only ErbB1 can trigger TLR3 signaling.\|There is a high degree of specificity of the targets of the two PTKs, EGFR and Src	SIGNOR-278932
P06493	P00533	1	phosphorylation	down-regulates	0.426	Using a synthetic peptide corresponding to the sequence surrounding ser-1002, p34cdc2 was identified as a kinase capable of phosphorylating this serine residue. phosphorylation of the egf receptor by p34cdc2 was associated with a decrease in its tyrosine protein kinase activity.	SIGNOR-38313
Q8TD19	Q8NHV4	1	phosphorylation	up-regulates activity	0.426	Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells.	SIGNOR-263016
O95476	Q13873	1	binding	down-regulates	0.426	We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors	SIGNOR-151001
P78527	P53350	2	phosphorylation	up-regulates activity	0.425	DNA-PKcs Promotes Plk1 Activation.\|Further analysis revealed that DNA-PKcs could directly phosphorylate the C-terminal PBD domain of Plk1 (lane 8).	SIGNOR-279562
Q9Y297	Q53EL6	1	ubiquitination	down-regulates	0.425	Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.	SIGNOR-160985
P06493	P46937	1	phosphorylation	up-regulates activity	0.425	Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.\|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis.	SIGNOR-276587
Q99835	P06241	1	phosphorylation	up-regulates	0.425	Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion.	SIGNOR-199156
Q13131	Q86TI0	1	phosphorylation	down-regulates	0.425	In rat l6 myotubes, endogenous tbc1d1 is strongly phosphorylated on ser237 and binds to 14-3-3s in response to the ampk activators aicar	SIGNOR-159048
P53350	P06748	1	phosphorylation	up-regulates	0.425	Phosphorylated at ser-4 by plk1 and plk2. Phosphorylation at ser-4 by plk2 in s phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at ser-4 by plk1 takes place during mitosis.	SIGNOR-125666
P06241	P20916	1	phosphorylation	up-regulates activity	0.425	Fyn constitutively binds to MAG in a latent form. Ligand stimulation of L-MAG would result in activation of Fyn kinase and phosphorylation of Tyr-620. Binding and activation of PLC y through this phosphotyrosine residue would contribute to the signaling pathway involved in the regulation of myelination.	SIGNOR-251178
Q99500	P08754	1	binding	up-regulates activity	0.425	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-257175
P04637	Q00653	1	binding	up-regulates	0.425	P52 cooperates with p53 to regulate other known p53 target genes.	SIGNOR-149811
Q86V15	Q9UHF1	1	transcriptional regulation	up-regulates quantity	0.425	We have recently demonstrated that a novel transcriptional pathway involving activation of the Epidermal Growth Factor-like Domain 7 (Egfl7) gene by the transcription factor CASTOR (CASZ1) is required for blood vessel assembly and lumen morphogenesis.	SIGNOR-266858
Q5VTR2	P36956	1	ubiquitination	down-regulates activity	0.425	Here, we reveal that RNF20-induced SREBP1c ubiquitination down-regulates hepatic lipogenic activity upon PKA activation.\|Overexpression of RNF20 represses SREBP1c activity, leading to a decrease in the expression of lipogenic genes.	SIGNOR-278643
O75444	P14921	1	binding	down-regulates	0.425	Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity.	SIGNOR-56808
P07550	P38405	1	binding	up-regulates activity	0.425	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-256952
Q16644	Q14457	1	phosphorylation	up-regulates activity	0.425	Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells.	SIGNOR-279342
Q13315	Q969H0	1	phosphorylation	up-regulates activity	0.425	In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7	SIGNOR-259942
Q9HC98	P0DMV8	1	phosphorylation	up-regulates activity	0.425	Mitotic phosphorylation of Hsp72 by the kinase NEK6 at Thr66 located in the NBD promotes the localization of Hsp72 to the mitotic spindle and is required for efficient spindle assembly and chromosome congression and segregation.	SIGNOR-273885
Q15154	P51955	1	relocalization	up-regulates	0.425	Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1	SIGNOR-133337

P05129

Q92686

1

phosphorylation

up-regulates activity

0.429

Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.

SIGNOR-248915

Q13882

P51692

1

phosphorylation

up-regulates

0.429

Phosphospecific antibodies, mutational analysis, and in vitro kinase assays demonstrated that brk specifically mediated stat5b phosphorylation at the activating tyrosine, y699.

SIGNOR-159066

Q13627

O95644

1

phosphorylation

up-regulates activity

0.429

DYRK1A phosphorylation of NFATc1 and alphaA at S261, S278, S403 and S409 interfered with NFATc1 ubiquitination and ubiquitin-proteasome degradation.|Here, we demonstrated that DYRK1A increased NFATc1 (NFATc1 and alphaA isoform) protein stability, in contrast to the decrease of NFATc2 protein stability by DYRK1A.

SIGNOR-278278

Q99835

P08754

1

binding

up-regulates

0.429

Consistent with its predicted topology, smo couples to a specific family of inhibitory g protein (gis) to regulate hh signaling.

SIGNOR-199165

P24941

P12830

1

phosphorylation

down-regulates quantity by destabilization

0.429

Priming phosphorylation of Cdh1 by the Cdk2/cyclin A kinase complex allows Plk1 to bind to Cdh1 and phosphorylate Cdh1 at Ser138 and Ser146. Phosphorylation of Cdh1 at Ser138 and Ser146 then triggers its interaction with, and subsequent ubiquitination by, SCFbeta-TRCP

SIGNOR-274049

Q13315

P53350

1

phosphorylation

down-regulates activity

0.429

Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5\u20137,18] , whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5\u201319] .|Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5-7,18], whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5-19].

SIGNOR-279793

P16234

Q05397

1

phosphorylation

up-regulates activity

0.429

Focal adhesion kinase (FAK) has a crucial role in integration of signals from integrins and growth factor receptors. In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor Met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate FAK on Tyr194 in the FERM domain (band 4.1 and ezrin/radixin/moesin homology domain). Upon binding to Met or phosphoinositides, FAK may undergo conformational changes, which renders Tyr194 accessible for phosphorylation. Substitution of Tyr194 with Phe significantly suppresses the activation of FAK by Met.

SIGNOR-259400

P04637

O15527

1

transcriptional regulation

up-regulates quantity by expression

0.429

Using gel-shift assays, we showed that p53 binds to its putative cis-elements within the hOGG1 promoter. In addition we demonstrated that supplementing p53 in HCT116p53-/- cells enhanced the transcription of hOGG1.

SIGNOR-255440

Q13287

P56693

1

binding

up-regulates activity

0.429

we identify an association of Sox10 with the N-myc interactor Nmi. Nmi modulated the transcriptional activity of Sox10 in reporter gene assays. Nmi effects varied between different Sox10 target gene promoters, indicating that Nmi function in vivo may be promoter-specific.

SIGNOR-225599

P17612

P48058

1

phosphorylation

up-regulates

0.429

We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus.

SIGNOR-97550

P24941

Q9Y618

1

phosphorylation

down-regulates activity

0.429

Cdk2 and Pin1 negatively regulate the transcriptional corepressor SMRT.|Cdk2 phosphorylates SMRT at consensus Cdk motifs to generate Pin1 binding sites and consequently targets SMRT for degradation, the latter also requiring the PPIase activity of Pin1 (XREF_FIG).

SIGNOR-278306

O15111

P04637

1

phosphorylation

up-regulates activity

0.429

In the nucleus, IKKalpha enhances p53 mediated GADD45 and BAD gene expressions by phosphorylating p53 at Ser20 and stabilizing p53 protein levels , leading to the induction of apoptosis in response to ROS exposure.|PKC-activated nuclear I\u03baB kinase\u03b1 promotes the stability of p53 protein and mediates reactive oxygen species-induced apoptosis [ ].

SIGNOR-280231

Q5VTB9

O75182

1

polyubiquitination

down-regulates quantity by destabilization

0.429

Here we identify RNF220 (RING finger protein 220) as a novel ubiquitin ligase for Sin3B. RNF220 specifically interacts with Sin3B both in vitro and in vivo. Sin3B can be regulated by the ubiquitin-proteasome system. Co-expression of RNF220 promotes the ubiquitination and proteasomal degradation of Sin3B.

SIGNOR-271943

Q15759

O60381

1

phosphorylation

up-regulates

0.428

A mutation of the p38 map kinase phosphorylation site at aa 401 [(s-a)401hbp1] also triggered hbp1 protein instability. While protein stability was compromised by mutation, the specific activities of (s-a)401hbp1 and of wild-type hbp1 appeared comparable for transcriptional repression.

SIGNOR-119134

P61088

Q12933

2

ubiquitination

up-regulates activity

0.428

Intact ring and zinc finger domains are required for tnfalfa-induced traf2 ubiquitination, which is also dependent on ubc13. Traf2 ubiquitination coincides with its translocation to the insoluble cellular fraction, resulting in selective activation of jnk. Ubc13 expression by rnai resulted in tnfalfa-induced traf2 translocation and impaired activation of jnk but not of ikk or p38.

SIGNOR-121274

P51608

Q8NFU7

1

binding

up-regulates activity

0.428

MeCP2 and its partners, splicing factor Y-box binding protein 1 (YB-1) and methylcytosine dioxygenase 1 (Tet1), bind to BDNF chromatin in naı ̈ve but dissociate during conditioning|Knockdown of MeCP2 shows it is instrumental for splicing and inhibits Tet1 and CTCF binding thereby negatively impacting DNA methylation and conditioning-dependent splicing regulation. Thus, mutations in MECP2 can have secondary effects on DNA methylation and alternative splicing.

SIGNOR-277701

P36897

Q9Y4K3

1

binding

up-regulates activity

0.428

We report here that TRAF6 is specifically required for the Smad-independent activation of JNK and p38 and its carboxyl TRAF homology domain physically interacts with TGF-² receptors

SIGNOR-241918

P49841

Q14596

1

phosphorylation

down-regulates activity

0.428

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261795

Q12933

P61088

2

binding

up-regulates activity

0.428

Traf2, ubc13, and ikkgamma were required for complex assembly and activation of mekk1 and mapk cascades.

SIGNOR-179479

P35367

P50148

1

binding

up-regulates activity

0.428

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-257376

Q9ULU8

P63027

1

binding

up-regulates activity

0.428

CAPS interactions with N-terminal regions of the SNARE motif of VAMP2 were also detected, which suggests that CAPS might recruit VAMP2 into syntaxin-1/SNAP-25 heterodimers for RQaQbc-SNARE complex assembly.

SIGNOR-264340

Q13555

Q9UQL6

1

phosphorylation

down-regulates

0.428

Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation.

SIGNOR-85102

P45983

O95140

1

phosphorylation

down-regulates quantity

0.428

We demonstrate that a critical component of the mitochondrial fusion apparatus, the mitofusin Mfn2, is a target for phosphorylation in response to a variety of cellular stresses. We provide direct evidence that JNK mediates this phosphorylation.

SIGNOR-274138

P42224

P35228

1

transcriptional regulation

up-regulates quantity by expression

0.428

STAT1 binds as a homodimer to cis elements known as gammaactivated sequences in the promoters of the genes encoding NOS2, the MHC class II transactivator (CIITA) and IL-12, among others.

SIGNOR-249497

Q16828

Q12778

1

dephosphorylation

up-regulates activity

0.428

It has been previously demonstrated that MKP-3 dephosphorylates FOXO1 on Ser256 and promotes nuclear translocation of FOXO1 , which subsequentially binds to the promoters of gluconeogenic genes and turns on the gluconeogenic program.|We also reported that MKP-3 can activate FOXO1 by at least dephosphorylating Ser 256, one of the Akt phosphorylation sites xref .

SIGNOR-276983

Q12778

P35558

1

transcriptional regulation

up-regulates quantity by expression

0.428

Phosphorylated foxo1 is inactive and retained in the cytosol. Mkp-3 mediated dephosphorylation activates foxo1 and subsequentially promotes its nuclear translocation and binding to the promoters of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (g6pase).

SIGNOR-197200

Q9BQ95

Q7Z434

1

binding

up-regulates activity

0.428

ECSIT interacts with IPS-1|ECSIT enhances IPS-1-mediated IFN-Beta promoter activation

SIGNOR-260371

Q14289

P40763

1

phosphorylation

up-regulates activity

0.428

These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).

SIGNOR-279429

P52333

Q15910

1

phosphorylation

up-regulates activity

0.428

These results demonstrate that phosphorylation of EZH2 by JAK3 on the Y244 increases the interaction with Polymerase II and decreases the association with PRC2 components promoting the expression of non-canonical genes.|To explore the mechanism of JAK3 mediated EZH2 activation, the authors performed co-immunoprecipitation assays, which revealed interaction of EZH2 with JAK3 and polymerase II.

SIGNOR-278518

Q8TD08

P05412

1

phosphorylation

up-regulates

0.428

Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation.

SIGNOR-91375

O60566

P25054

1

phosphorylation

up-regulates activity

0.428

These findings support a model in which BubR1 kinase may directly regulate APC function involved in stable kinetochore microtubule attachment.|Using purified components, BubR1 directly phosphorylates APC and forms a ternary complex with APC and microtubules.

SIGNOR-279393

Q8TAU0

Q13477

1

transcriptional regulation

up-regulates quantity by expression

0.428

We provide evidence that NKX2.3 can activate MAdCAM-1 transcription directly

SIGNOR-266219

P00558

Q15118

1

phosphorylation

up-regulates activity

0.428

Mitochondrial PGK1 acts as a protein kinase to phosphorylate pyruvate dehydrogenase kinase 1 (PDHK1) at T338, which activates PDHK1 to phosphorylate and inhibit the pyruvate dehydrogenase (PDH) complex.

SIGNOR-278365

P27361

P10828

1

phosphorylation

down-regulates activity

0.428

We concluded that serine 142 of the tr dbd is the likely site of phosphorylation by t(4)-activated mapk and that the docking site on tr for activated mapk includes residues 128-133 (kgffrr), a basic amino acid-enriched motif novel for mapk substrates. Tr mutations in the proposed mapk docking domain and at residue 142 modulated t(4)-conditioned shedding of co-repressor and recruitment of co-activator proteins by the receptor, and they altered transcriptional activity of tr in a thyroid hormone response element-luciferase reporter assay.

SIGNOR-102224

P31749

Q16875

1

phosphorylation

up-regulates

0.427

We also found that AMP activated protein kinase and protein kinases A, B, and C catalyzed the phosphorylation of Ser-460 of HBP1, and that in addition both isoforms are phosphorylated at a second, as yet undetermined site by protein kinase C. However, none of the phosphorylations had any effect on the intrinsic kinetic characteristics of either enzymatic activity, and neither did point mutation (mimicking phosphorylation), deletion, and alternative-splice modification of the HBP1 carboxy-terminal region. Instead, these phosphorylations and mutations decreased the sensitivity of the 6PF2K to a potent allosteric inhibitor, phosphoenolpyruvate, which appears to be the major regulatory mechanism.

SIGNOR-252477

P53350

O95271

1

phosphorylation

up-regulates quantity by stabilization

0.427

Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends.

SIGNOR-276245

Q13627

P10636

1

phosphorylation

down-regulates

0.427

Dyrk1a phosphorylates tau at least at s202, t212 and s404, but t212 phosphorylation is known to initiate tau hyperphosphorylation by gsk3b (ryoo et al., 2007;woods et al., 2001) and has been demonstrated to have a role in alternative splicing of taumrna

SIGNOR-171030

Q15759

P05787

1

phosphorylation

up-regulates

0.427

Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.

SIGNOR-114063

Q8NEZ5

P35613

1

ubiquitination

down-regulates quantity by destabilization

0.427

F-Box Protein FBXO22 Mediates Polyubiquitination and Degradation of CD147 to Reverse Cisplatin Resistance of Tumor Cells

SIGNOR-273452

Q9UQM7

P14136

1

phosphorylation

down-regulates activity

0.427

On the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did induce disassembly of the filament. Sequential analysis of the purified phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2 kinase, whereas Ser13, Ser17, Ser34, and Ser389 on GFAP were phosphorylated by Ca(2+)-CaM-dependent protein kinase II.

SIGNOR-250626

Q96EP1

P09874

1

polyubiquitination

down-regulates quantity by destabilization

0.427

Here, we show that checkpoint with Forkhead-associated (FHA) and RING finger domain protein (CHFR), an E3 ubiquitin ligase, is recruited to DSBs by poly(ADP-ribose) (PAR). Moreover, CHFR ubiquitinates PAR polymerase 1 (PARP1) and regulates chromatin-associated PARP1 in vivo. Moreover, the poly-ubiquitin chain on PARP1 could be recognized by both anti-K48 and K63-linked poly-ubiquitin chain antibodies, suggesting that CHFR mediates a mixed poly-ubiquitin chain linkage on PARP1. With MG132 treatment, ubiquitinated PARP1 was significantly accumulated (Figure 4D), suggesting that the ubiquitination of PARP1 is likely involved in protein degradation. Consistently, we found that following DNA damage, PARP1 quickly dissociated from the chromatin in the wild-type cells (Figure 4F). However, in the Chfr−/− cells, the dissociation of PARP1 from the chromatin was significantly delayed.

SIGNOR-271470

Q99523

P02649

1

binding

up-regulates quantity

0.427

Here, we identified the pro-neurotrophin receptor sortilin as major endocytic pathway for clearance of APOE/Aβ complexes in neurons. Sortilin binds APOE with high affinity. Lack of receptor expression in mice results in accumulation of APOE and of Aβ in the brain and in aggravated plaque burden. Sortilin interacts with all human APOE isoforms.

SIGNOR-273721

Q13043

P98177

1

phosphorylation

up-regulates

0.427

The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1

SIGNOR-178193

Q92834

P61006

1

guanine nucleotide exchange factor

up-regulates activity

0.427

PGR interacts with the small GTPase RAB8A, which participates in cilia biogenesis and maintenance. We show that RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange. RPGR functions as a GEF for RAB8A and RPGR–RAB8A association may facilitate ciliary trafficking.

SIGNOR-253030

P20749

Q13547

1

binding

up-regulates

0.427

We show that bcl-3 is a substrate for the protein kinase gsk3 and that gsk3-mediated bcl-3 phosphorylation, which is inhibited by akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with hdac1, -3, and -6

SIGNOR-129801

O43426

Q12965

1

binding

up-regulates activity

0.427

We describe binding of two PRD-containing endocytic proteins, dynamin and synaptojanin-1, to the SH3 domain of Myo1E. This interaction was detected both in vitro, using pull-downs of purified proteins, and in vivo, using immunoprecipitation of protein complexes from synapse-enriched brain extract and immunolocalization of Myo1E and dynamin. Our observation of the interaction between human Myo1E and endocytic proteins suggests that this longtailed myosin may play a role in clathrin-dependent endocytosis.Interaction between Myo1E SH3 domain and PRD-containing endocytic proteins may promote recruitment of Myo1E to clathrin-coated structures since an inactivating mutation in the SH3 domain reduced Myo1E localization to clathrin-containing puncta.

SIGNOR-265423

Q8N9B8

P01116

1

guanine nucleotide exchange factor

up-regulates

0.427

Gefs catalyse the transition from gdp-bound, inactive ras to gtp-bound, active ras.

SIGNOR-183826

Q5H9F3

P56524

1

binding

up-regulates activity

0.427

BCoR-L1 interacts with Class II HDACs, HDAC4, HDAC5, and HDAC7, suggesting that they are involved in its function as transcriptional corepressor.

SIGNOR-259112

P85298

P61586

1

gtpase-activating protein

down-regulates activity

0.427

We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).

SIGNOR-260463

P68400

Q8IVP5

1

phosphorylation

down-regulates activity

0.427

Here, we identify that the mitochondrially localized PGAM5 phosphatase interacts with and dephosphorylates FUNDC1 at serine 13 (Ser-13) upon hypoxia or carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP) treatment. Dephosphorylation of FUNDC1 catalyzed by PGAM5 enhances its interaction with LC3, which is abrogated following knockdown of PGAM5 or the introduction of a cell-permeable unphosphorylated peptide encompassing the Ser-13 and LIR of FUNDC1. We further observed that CK2 phosphorylates FUNDC1 to reverse the effect of PGAM5 in mitophagy activation.

SIGNOR-273622

Q99728

P03372

1

ubiquitination

down-regulates quantity

0.427

As shown in xref , both FOXK2 and BARD1 enhanced the ubiquitination of ER\u03b1, with the extent of ubiquitination being enhanced when both FOXK2 and BARD1 were overexpressed.|These findings suggested that FOXK2 might act as a negative regulator of Estrogen receptor\u03b1, and its association with both Estrogen receptor\u03b1 and BRCA1/BARD1 could lead to the down-regulation of Estrogen receptor\u03b1 transcriptional activity, effectively regulating the function of Estrogen receptor\u03b1.

SIGNOR-278803

P07237

O75460

1

binding

down-regulates activity

0.427

The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.

SIGNOR-275573

P36956

Q8NBP7

1

transcriptional regulation

up-regulates quantity by expression

0.427

Expression of nuclear forms of sterol-regulatory element binding protein-1 (SREBP-1) and SREBP-2 dramatically increased the promoter activity of PCSK9.

SIGNOR-255222

P23760

Q9UJU2

1

binding

up-regulates activity

0.427

Pax3 binds to lef1 pax3 activity may directly effect the expression of factors regulated by signal transduction pathways dependent on lef1.

SIGNOR-162100

Q07912

P31749

1

phosphorylation

up-regulates activity

0.427

Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.

SIGNOR-252446

P45983

P31749

1

phosphorylation

up-regulates activity

0.427

We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase.

SIGNOR-252426

P67775

P23396

1

dephosphorylation

down-regulates

0.427

We identified that pp2a interacts with wild-type rps3, but not with mutants (s6a/t221a) (fig. 8), and that it associates with the n-terminal region of rps3 (fig. 2). From our results presented here, we conclude that pp2a is involved in the dephosphorylation of phosphorylated rps3 by pkc, and that serine 6 on the n-terminal region of rps3 appears to mediate the pp2a recruitment.

SIGNOR-137963

P62136

P31749

1

dephosphorylation

down-regulates activity

0.426

Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells

SIGNOR-252603

O60885

Q09472

1

binding

up-regulates activity

0.426

In this study, we explored the role of Brd4 and its interaction with the p300 acetyltransferase in the regulation of Nox4 and the in vivo efficacy of a BET inhibitor to reverse established age-associated lung fibrosis. |Together, these studies suggest that Brd4 enhances p300-mediated histone acetylation.

SIGNOR-262064

P27361

Q9UBN7

1

phosphorylation

up-regulates

0.426

Histone deacetylase 6 (hdac6) is well known for its ability to promote cell migrationextracellular signal-regulated kinase (erk) phosphorylates histone deacetylase 6 (hdac6) at serine 1035 to stimulate cell migrationwe have identified two novel erk-mediated phosphorylation sites: threonine 1031 and serine 1035 in hdac6. Both sites were phosphorylated by erk1

SIGNOR-202702

Q8IXJ6

P35558

1

deacetylation

up-regulates quantity by stabilization

0.426

Conversely, SIRT2 deacetylates and stabilizes PEPCK1.|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1

SIGNOR-267599

Q9ULB1

Q14118

1

binding

up-regulates activity

0.426

The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.

SIGNOR-265458

P58400

Q14118

1

binding

up-regulates activity

0.426

The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM.

SIGNOR-265459

P24941

P29374

1

phosphorylation

down-regulates

0.426

In the present study we identified rbp1 as a novel cdk substrate. Rbp1 is phosphorylated by cdk2 on serines 864 and 1007, which are n- and c-terminal to the lxcxe motif, respectively. Cdk2-mediated phosphorylation of rbp1 or prb destabilizes their interaction in vitro, with concurrent phosphorylation of both proteins leading to their dissociation

SIGNOR-170455

P47900

P30679

1

binding

up-regulates activity

0.426

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-257339

P31751

P15336

1

phosphorylation

up-regulates activity

0.426

Taken together, these data suggest that AMPK regulates EC migration through phosphorylation of AKT2, which promotes ATF2 transactivation of MMP-2 during EC migration.|Within this subgroup, we chose AKT2 for analysis because AKT2 phosphorylates activating transcription factor 2 (ATF2) [ xref , xref ].

SIGNOR-280178

Q16539

P24385

1

phosphorylation

up-regulates

0.426

A large number of cytosolic proteins can be phosphorylated by p38 mapks, including phospholipase a2, the microtubule-associated protein tau, nhe-1, cyclin d1, cdk inhibitors, bcl2 family proteins, growth factor receptors or keratins

SIGNOR-166594

Q16236

P04040

1

transcriptional regulation

up-regulates quantity by expression

0.426

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254651

Q99684

P14921

2

binding

down-regulates activity

0.426

Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.

SIGNOR-254201

Q13546

Q5VWQ8

1

phosphorylation

up-regulates activity

0.426

We further show that RIP1 (the Ser/Thr protein kinase receptor-interacting protein) associates with the GAP domain of AIP1 and mediates TNF-induced AIP1 phosphorylation at Ser-604 and JNK/p38 activation as demonstrated by both overexpression and small interfering RNA knockdown of RIP1 in EC.

SIGNOR-259976

P46531

P15923

1

binding

down-regulates

0.426

We provide evidence that notch and deltex may act on e47 by inhibiting signaling through ras because (i) full e47 activity was found to be dependent on ras and (ii) both notch and deltex inhibited gal4-jun, a hybrid transcription factor whose activity is dependent on signaling from ras to sapk/jnk.

SIGNOR-56150

P10586

P07949

1

dephosphorylation

down-regulates

0.426

Lar expression significantly reduced tyrosine-1062 phosphorylation in ret-men2a but not in ret-men2b

SIGNOR-85170

P12931

P13688

1

phosphorylation

up-regulates activity

0.426

Recent reports have also suggested that Bgp1 behaves as a signal transduction molecule. Several physiological events promote the Tyr phosphorylation of Bgp1 on one or two Tyr residues within its cytoplasmic domain (Tyr-488 and Tyr-515). BGP becomes Tyr-phosphorylated by Src-like Tyr kinases in activated neutrophils (24) and in human colon carcinoma cellsWe have recently shown that Tyr phosphorylation of the mouse Bgp1 cytoplasmic domain in CT51 mouse colonic carcinoma cells led to its binding to the protein-Tyr phosphatase SHP-1 and that this event required the presence of both Tyr-488 and Tyr-515

SIGNOR-246471

P14921

Q99684

2

binding

down-regulates activity

0.426

Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent manner.

SIGNOR-254202

P30411

P30679

1

binding

up-regulates activity

0.426

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-257281

P18847

Q99988

1

transcriptional regulation

up-regulates quantity by expression

0.426

In addition, DIM increased the expression of NAG-1 as well as activating transcription factor 3 (ATF3), and the induction of ATF3 was earlier than that of NAG-1. The DIM treatment increased luciferase activity of NAG-1 in HCT-116 cells transfected with NAG-1 promoter construct. The results suggest that I3C represses cell proliferation through up-regulation of NAG-1 and that ATF3 may play a pivotal role in DIM-induced NAG-1 expression in human colorectal cancer cells.

SIGNOR-253725

O14578

Q9NQS7

1

phosphorylation

up-regulates activity

0.426

Figure 5.CIT-K phosphorylates INCENP. (a) Schematic diagram of INCENP structure illustrating the phosphorylated sites identified by MS.

SIGNOR-280232

Q13418

Q13765

1

phosphorylation

up-regulates

0.426

Ilk phosphorylated alpha-nac on residue ser-43. Ilk-dependent phosphorylation of alpha-nac induced the nuclear accumulation of the coactivator and that phosphorylation of alpha-nac by ilk is required for the potentiation of c-jun-mediated responses by the kinase.

SIGNOR-127694

Q13418

E9PAV3

1

phosphorylation

up-regulates

0.426

The inactivation of gsk3? In response to adhesion and ilk activation (6) would then result in a thr-159-hypophosphorylated ?-Nac that would become unavailable for proteasome degradation but would become a substrate for the ilk kinase activity on residue ser-43. The ser-43-phosphorylated ?-Nac would preferentially interact with c-jun (30), translocate to the nucleus, and potentiate transcription

SIGNOR-127631

P00533

O15455

1

phosphorylation

up-regulates activity

0.426

Although both the ErbB1 and the ErbB2 isoforms of EGFR can bind to activated TLR3, functionally, only ErbB1 can trigger TLR3 signaling.|There is a high degree of specificity of the targets of the two PTKs, EGFR and Src

SIGNOR-278932

P06493

P00533

1

phosphorylation

down-regulates

0.426

Using a synthetic peptide corresponding to the sequence surrounding ser-1002, p34cdc2 was identified as a kinase capable of phosphorylating this serine residue. phosphorylation of the egf receptor by p34cdc2 was associated with a decrease in its tyrosine protein kinase activity.

SIGNOR-38313

Q8TD19

Q8NHV4

1

phosphorylation

up-regulates activity

0.426

Nek9 phosphorylates NEDD1 on Ser377 driving its recruitment and thereby that of γ-tubulin to the centrosome in mitotic cells.

SIGNOR-263016

O95476

Q13873

1

binding

down-regulates

0.426

We show that dullard promotes the ubiquitin-mediated proteosomal degradation of bmp receptors

SIGNOR-151001

P78527

P53350

2

phosphorylation

up-regulates activity

0.425

DNA-PKcs Promotes Plk1 Activation.|Further analysis revealed that DNA-PKcs could directly phosphorylate the C-terminal PBD domain of Plk1 (lane 8).

SIGNOR-279562

Q9Y297

Q53EL6

1

ubiquitination

down-regulates

0.425

Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.

SIGNOR-160985

P06493

P46937

1

phosphorylation

up-regulates activity

0.425

Our evidence suggested that these YAP sites (Ser138, Thr143, and Ser367) were CDK1 phosphorylation sites.|These data demonstrate that the YAP phosphorylation sites Ser138, Thr143, and Ser367 are important for proper mitosis and cytokinesis.

SIGNOR-276587

Q99835

P06241

1

phosphorylation

up-regulates

0.425

Instead, shh rapidly and locally stimulated phosphorylation of the src family kinase (sfk) members src and fyn in a smo-dependent fashion.

SIGNOR-199156

Q13131

Q86TI0

1

phosphorylation

down-regulates

0.425

In rat l6 myotubes, endogenous tbc1d1 is strongly phosphorylated on ser237 and binds to 14-3-3s in response to the ampk activators aicar

SIGNOR-159048

P53350

P06748

1

phosphorylation

up-regulates

0.425

Phosphorylated at ser-4 by plk1 and plk2. Phosphorylation at ser-4 by plk2 in s phase is required for centriole duplication and is sufficient to trigger centriole replication. Phosphorylation at ser-4 by plk1 takes place during mitosis.

SIGNOR-125666

P06241

P20916

1

phosphorylation

up-regulates activity

0.425

Fyn constitutively binds to MAG in a latent form. Ligand stimulation of L-MAG would result in activation of Fyn kinase and phosphorylation of Tyr-620. Binding and activation of PLC y through this phosphotyrosine residue would contribute to the signaling pathway involved in the regulation of myelination.

SIGNOR-251178

Q99500

P08754

1

binding

up-regulates activity

0.425

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-257175

P04637

Q00653

1

binding

up-regulates

0.425

P52 cooperates with p53 to regulate other known p53 target genes.

SIGNOR-149811

Q86V15

Q9UHF1

1

transcriptional regulation

up-regulates quantity

0.425

We have recently demonstrated that a novel transcriptional pathway involving activation of the Epidermal Growth Factor-like Domain 7 (Egfl7) gene by the transcription factor CASTOR (CASZ1) is required for blood vessel assembly and lumen morphogenesis.

SIGNOR-266858

Q5VTR2

P36956

1

ubiquitination

down-regulates activity

0.425

Here, we reveal that RNF20-induced SREBP1c ubiquitination down-regulates hepatic lipogenic activity upon PKA activation.|Overexpression of RNF20 represses SREBP1c activity, leading to a decrease in the expression of lipogenic genes.

SIGNOR-278643

O75444

P14921

1

binding

down-regulates

0.425

Full-length c-maf binds to the c-myb and ets-1. / c-maf inhibits c-myb and ets-1 transcriptional activity.

SIGNOR-56808

P07550

P38405

1

binding

up-regulates activity

0.425

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-256952

Q16644

Q14457

1

phosphorylation

up-regulates activity

0.425

Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells.

SIGNOR-279342

Q13315

Q969H0

1

phosphorylation

up-regulates activity

0.425

In response to ionizing radiation, ATM phosphorylates FBXW7 at serine 26 to recruit it to DNA double-strand break (DSB) sites, whereas activated DNA-PKcs phosphorylates XRCC4 at serines 325/326, which promotes binding of XRCC4 to FBXW7

SIGNOR-259942

Q9HC98

P0DMV8

1

phosphorylation

up-regulates activity

0.425

Mitotic phosphorylation of Hsp72 by the kinase NEK6 at Thr66 located in the NBD promotes the localization of Hsp72 to the mitotic spindle and is required for efficient spindle assembly and chromosome congression and segregation.

SIGNOR-273885

Q15154

P51955

1

relocalization

up-regulates

0.425

Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1

SIGNOR-133337