GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 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
P07550	O95837	2	binding	up-regulates activity	0.314	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-257192
Q16236	P05771	0	phosphorylation	up-regulates	0.418	Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress	SIGNOR-91830
Q00987	O15151	2	ubiquitination	down-regulates	0.733	The mdm2 homolog mdmx is an important regulator of p53 during mouse embryonic development. Dna damage promotes mdmx phosphorylation, nuclear translocation, and degradation by mdm2.	SIGNOR-144970
P68400	Q13829	1	phosphorylation	up-regulates	0.2	It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions.	SIGNOR-188849
O75116	O14950	1	phosphorylation	up-regulates activity	0.598	In addition, an in vitro kinase assay with mixed recombinant GST-ROCK2 and MLC2 revealed that ROCK2 phosphorylated WT MLC2, but not MLC2 S15A mutant, indicating that it phosphorylates MLC2 at S15 in vitro (XREF_FIG).	SIGNOR-279103
Q13362	O96017	0	phosphorylation	up-regulates	0.322	Found that chk2 associated with the b' regulatory subunit of protein phosphatase pp2a. In vitro kinase assays showed that b'gamma3 was a potent chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of pp2a.	SIGNOR-129255
Q9NZN5	Q05397	0	phosphorylation	up-regulates activity	0.303	These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa.	SIGNOR-279310
Q16665	P15692	1	transcriptional regulation	up-regulates quantity	0.773	Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription.	SIGNOR-256592
P42574	P09874	1	cleavage	down-regulates activity	0.775	Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process	SIGNOR-116178
P29353	P14784	2	binding	up-regulates	0.558	The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival	SIGNOR-204975
P32238	P30679	2	binding	up-regulates activity	0.485	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-257410
Q8TAF3	O94782	2	binding	up-regulates activity	0.946	In vitro reconstitution of USP1 deubiquitinating enzyme activity, using either ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) or purified monoubiquitinated FANCD2 protein as substrates, demonstrates that UAF1 functions as an activator of USP1. UAF1 binding increases the catalytic turnover (kcat) but does not increase the affinity of the USP1 enzyme for the substrate (KM).	SIGNOR-263274
P22681	Q9BX66	2	binding	up-regulates	0.688	Cbl is recruited to the insulin receptor by interaction with the adapter protein cap, through one of three adjacent sh3 domains in the carboxy terminus of cap	SIGNOR-82283
O95198	Q9BYP7	2	binding	down-regulates quantity by destabilization	0.476	We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.	SIGNOR-272121
O60641	P63027	2	binding	up-regulates quantity	0.63	the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval.	SIGNOR-264112
P41091	Q9UI10	0	guanine nucleotide exchange factor	up-regulates activity	0.698	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269137
P31269	O43189	0	transcriptional regulation	down-regulates quantity by repression	0.286	These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.	SIGNOR-260069
P42229	Q9NSE2	1	transcriptional regulation	up-regulates quantity by expression	0.669	The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD	SIGNOR-261544
P35712	Q14669	0	ubiquitination	down-regulates quantity by destabilization	0.397	In this article, we focused on Trip 12, an E3 ubiquitin ligase, which polyubiquitinates Sox6.\|Therefore, Sox6 is a specific substrate to Trip12, by which it is polyubiquitinated and degraded.	SIGNOR-278579
P35968	P12931	0	phosphorylation	up-regulates activity	0.614	In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).\|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).	SIGNOR-279120
Q99081	Q02535	2	binding	down-regulates activity	0.466	All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.	SIGNOR-241152
P06730	P17252	0	phosphorylation	up-regulates	0.382	Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .	SIGNOR-248945
P10586	Q13136	0	relocalization	up-regulates activity	0.8	We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions.	SIGNOR-264141
P32121	P07550	2	binding	down-regulates activity	0.724	The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors	SIGNOR-256501
P12830	Q9UQB3	2	binding	up-regulates quantity by stabilization	0.447	To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.	SIGNOR-252134
Q05209	O43586	1	dephosphorylation	down-regulates activity	0.61	We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. \|The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.\|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl	SIGNOR-248656
Q8NHZ8	O95835	0	phosphorylation	up-regulates activity	0.466	LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C\|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C\|Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly	SIGNOR-275472
O15105	P84022	1	transcriptional regulation	down-regulates quantity	0.613	The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression	SIGNOR-260437
Q5TZA2	P24941	0	phosphorylation	down-regulates	0.2	Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway.	SIGNOR-197593
Q15418	P49815	1	phosphorylation	down-regulates	0.768	The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1	SIGNOR-128634
P84550	P52954	2	binding	down-regulates activity	0.558	Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord.	SIGNOR-238004
P15056	P36507	1	phosphorylation	up-regulates	0.75	We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l.	SIGNOR-42664
Q9UPT5	P28482	0	phosphorylation	up-regulates	0.331	Erk1/2 phosphorylation enhances the binding of exo70 to other exocyst components and promotes the assembly of the exocyst complex in response to epidermal growth factor (egf) signaling.	SIGNOR-197543
Q9ULU4	P03956	1	transcriptional regulation	down-regulates quantity by repression	0.2	Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported	SIGNOR-262042
P05787	P06493	0	phosphorylation	up-regulates	0.248	With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.	SIGNOR-56054
Q99683	O75460	1	phosphorylation	up-regulates activity	0.618	ASK1 may directly phosphorylate IRE1\u03b1 at sites other than the IRE1\u03b1 autophosphorylation site.	SIGNOR-279213
P33991	Q13535	0	phosphorylation	up-regulates	0.724	Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.	SIGNOR-169412
Q05655	P51398	1	phosphorylation	up-regulates	0.2	Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3	SIGNOR-160488
P17612	Q9Y698	1	phosphorylation	down-regulates activity	0.432	phosphorylation of stargazin at T321 by PKA inhibits its interaction with PSD-95.	SIGNOR-250342
Q13635	O94991	2	binding	down-regulates activity	0.2	SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation.	SIGNOR-268438
P23467	P08581	1	dephosphorylation	down-regulates	0.364	Ptp1b and shp-2 are bound to the c-met receptor to control its activity. Although the binding of ptp1b increases when there is a decrease in c-met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of shp-2 coincide with maximal stimulation of c-met, acting as a positive regulator.	SIGNOR-139560
P42681	P06241	0	phosphorylation	up-regulates activity	0.347	We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.	SIGNOR-249341
P25025	P42830	2	binding	up-regulates activity	0.752	CXCL5 is another ELR+ CXC chemokine and, thus, also potently attracts neutrophils. Just like CXCL1, CXCL5 also signals through CXCR2, explaining why, often, CXCL5 and CXCL1 are seen to function in parallel in PDAC. CXCL5 was increased in human pancreatic tissue compared to the normal pancreas, and the knockdown of CXCL5 in pancreatic cancer cell lines reduced the proliferation and migration ability of cells	SIGNOR-277730
Q15418	P30305	1	phosphorylation	up-regulates	0.253	Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.	SIGNOR-202125
Q2TAL8	O95363	1	transcriptional regulation	up-regulates quantity by expression	0.2	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269403
Q13635	P42574	0	cleavage	down-regulates	0.321	Like other dependence receptors, ptc1 contains a dependence-as-associated receptor c-terminal motif that is cleaved by caspases at a conserved aspartic acid (asp 1392) in the absence of shh, to expose a proapoptotic domain.	SIGNOR-199111
Q8TDC3	P30307	1	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
Q13153	Q13153	2	phosphorylation	up-regulates activity	0.2	Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation.	SIGNOR-250219
Q9UPZ9	Q8N122	1	phosphorylation	up-regulates	0.2	Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.	SIGNOR-196198
P68400	P08575	1	phosphorylation	up-regulates	0.442	Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,	SIGNOR-65277
O00533	Q12955	1	relocalization	up-regulates quantity	0.412	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266723
P28482	Q969V6	1	phosphorylation	down-regulates	0.2	Serum induces rhoa-dependent translocation of mkl1 from the cytoplasm to the nucleus and also causes a rapid increase in mkl1 phosphorylation. Serum-induced phosphorylation of the serum response factor coactivator mkl1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization.	SIGNOR-195153
Q9Y5I2	Q9Y5G0	2	binding	up-regulates activity	0.2	The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.	SIGNOR-265714
Q9UQL6	P17612	0	phosphorylation	up-regulates activity	0.2	PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex	SIGNOR-198658
P45983	Q16828	0	dephosphorylation	down-regulates activity	0.632	Our data demonstrate MKP-3 has differential substrate preference in astrocytes compared to other cells types, since it preferentially dephosphorylated p-JNK over p-ERK.\|The main findings of our studies are (1) MKP-3 preferentially reduces p-JNK over p-ERK and p-p38 in primary astrocytes; (2) This MAPK modulation pattern in primary astrocytes significantly reduced NO and completely abolished IL-6 and TNF accumulation; and (3) These effects are specifically induced by MKP-3 since block-age of MKP-3 mRNA expression reversed its action on MAPKs and pro-inflammatory mediators in BV-2 microglia cells.	SIGNOR-277150
P17252	Q13769	1	phosphorylation	up-regulates	0.327	We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.	SIGNOR-126572
O00418	Q13131	0	phosphorylation	down-regulates activity	0.492	AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase	SIGNOR-250314
Q06187	Q03113	2	binding	up-regulates activity	0.317	Here we show that Ga12 binds directly to, and stimulates the activity of, Bruton’s tyrosine kinase (Btk) and a Ras GTPase-activating protein, Gap1m, in vitro and in vivo	SIGNOR-278082
Q70YC5	P09874	2	binding	up-regulates activity	0.2	We identified ZNF365 as a necessary component of the HR repair pathway. ZNF365 interacts with PARP1 and tethers MRE11 to the nucleolytic resection sites for replication fork recovery	SIGNOR-272477
Q16539	P49137	1	phosphorylation	up-regulates activity	0.769	Here we show that in vitro rk phosphorylates human gst-mapkap kinase-2 at thr25 in the proline-rich n-terminal region thr222 and ser272 in the catalytic domain and thr334 in the c-terminal domain. Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation	SIGNOR-44351
P51955	P35222	1	phosphorylation	down-regulates quantity	0.469	NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.\|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).	SIGNOR-278173
P12931	P52757	1	phosphorylation	down-regulates	0.2	Here we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). Mutational analysis identified tyr-21 in the n-terminal regulatory region as a major phosphorylation site. these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity.	SIGNOR-155713
O00744	Q13467	2	binding	up-regulates	0.619	Inhibition of adipogenesis by wnt10b is likely mediated by‚ wnt‚ receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 8	SIGNOR-210164
Q9UBP0	P53990	0	relocalization	up-regulates activity	0.519	Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.	SIGNOR-269047
P12318	P06241	0	phosphorylation	up-regulates activity	0.534	To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point\|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.	SIGNOR-249336
P63096	P28221	2	binding	up-regulates activity	0.435	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-256721
P49715	P49675	1	transcriptional regulation	up-regulates quantity by expression	0.335	Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells.	SIGNOR-254043
Q9GZV5	Q9NRM7	0	phosphorylation	down-regulates	0.698	Activated lats1/2 in turn phosphorylate and inhibit yap/taz transcription co-activators	SIGNOR-175787
P54753	Q15768	2	binding	up-regulates	0.821	Ephrin-b3, a ligand for the receptor ephb3, expressed at the midline of the developing neural tube.	SIGNOR-54711
P07550	P38405	2	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
P03951	P00748	0	cleavage	up-regulates activity	0.494	Activation of factor XI in plasma is dependent on factor XII \| Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.	SIGNOR-263519
Q7L2J0	Q6NYC1	0	cleavage	down-regulates activity	0.268	JMJD6 cleaves MePCE. we propose that JMJD6 is the cognate protease of MePCE and cleaves at the R171 site within MePCE. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II.	SIGNOR-261037
Q96BR1	Q86YD1	1	phosphorylation	down-regulates quantity by destabilization	0.2	In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.	SIGNOR-279283
P19484	Q9GZQ8	1	transcriptional regulation	up-regulates quantity by expression	0.391	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276559
Q99706	P17693	2	binding	up-regulates	0.764	Recombinant soluble kir2dl4 binds to cells expressing hla-g but not to cells expressing other hla class i molecules.	SIGNOR-66132
P40763	P43378	0	dephosphorylation	down-regulates activity	0.432	Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.\|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.\|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.	SIGNOR-276976
Q9UNE7	Q86WG3	1	polyubiquitination	down-regulates quantity by destabilization	0.378	CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.	SIGNOR-272651
Q9BV47	Q13158	1	dephosphorylation	down-regulates activity	0.366	This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation	SIGNOR-204559
P29474	Q14289	0	phosphorylation	down-regulates	0.309	We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.	SIGNOR-161824
O60216	P04114	1	transcriptional regulation	down-regulates quantity	0.2	The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.	SIGNOR-259974
P49841	P11388	1	phosphorylation	down-regulates quantity by destabilization	0.348	This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.	SIGNOR-276301
P14653	P40424	2	binding	up-regulates activity	0.807	Pbx1 and exd act as cofactors that enhance the DNA binding specificity of Hox proteins. The structure of the HoxB1Pbx1DNA ternary complex shows that HoxB1 and Pbx1 bind to overlapping binding sites located on opposite faces of the DNA.	SIGNOR-241219
P06493	P18031	1	phosphorylation	up-regulates activity	0.502	Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.\|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.	SIGNOR-272970
P24941	P26358	1	phosphorylation	up-regulates	0.342	We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5	SIGNOR-173681
P04406	Q13043	0	phosphorylation	up-regulates activity	0.279	Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.\|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.	SIGNOR-279295
P25963	Q04206	2	binding	up-regulates activity	0.891	Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b.	SIGNOR-17691
O75582	P19419	1	phosphorylation	up-regulates	0.2	Phosphorylation on ser383 and ser389 of elk-1 by mapk enhances this basal binding but, most importantly, elk-1 exhibits new interactions with p300.	SIGNOR-85514
P55211	O15392	2	binding	down-regulates	0.504	Survivin (an inhibitor of apoptosis) phosphorylation on thr34 may regulate apoptosis at cell division via an interaction with caspase-9.	SIGNOR-84065
O00141	Q13164	0	phosphorylation	up-regulates	0.388	Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.	SIGNOR-105728
Q96BK5	P53350	0	phosphorylation	down-regulates	0.361	Here, we show that polo-like kinase 1 (plk1) is a novel interacting protein of pinx1. Plk1 interacts with and phosphorylates pinx1 in vivo and in vitro. Moreover, plk1-mediated phosphorylation of pinx1 at five phosphorylation sites is essential for its plk1-induced degradation.	SIGNOR-166333
Q9UH17	P17612	0	phosphorylation	down-regulates activity	0.2	Here we show that protein kinase A (PKA) physically binds to A3B and phosphorylates Thr214.	SIGNOR-277455
P31276	P55268	1	transcriptional regulation	up-regulates quantity by expression	0.2	The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.	SIGNOR-261644
Q8IWU2	P13569	1	phosphorylation	down-regulates activity	0.401	The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.\|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.	SIGNOR-278227
P09211	P17252	0	phosphorylation	up-regulates activity	0.2	Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently	SIGNOR-276024
P06241	Q9UQC2	1	phosphorylation	up-regulates activity	0.605	Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.\|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2.	SIGNOR-279984
P24385	P03372	0	transcriptional regulation	up-regulates quantity by expression	0.754	Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1.	SIGNOR-135053
P49674	Q92997	2	phosphorylation	down-regulates activity	0.669	Co-expression of CK1ϵ with FLAG-Dvl3 retards electrophoretic migration and induces phosphorylation-dependent shift of Dvl (PS-Dvl3). mutations of Ser-280 and Ser-311 prevent efficient activation of Wnt/β-catenin by Dvl3.	SIGNOR-276645
Q8N2W9	P42224	2	binding	down-regulates	0.561	First, piasy interacts with stat1 both in vitro and in vivo. The in vivo piasy__stat1 interaction is dependent on cytokine stimulation. Second, piasy can inhibit stat1-mediated gene activation without blocking the dna binding activity of stat1.	SIGNOR-105723
Q02388	P13497	0	cleavage	up-regulates quantity	0.604	We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA/DTAG within the NC-2 domain. Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen.	SIGNOR-256338
Q9BY78	Q86WV6	1	ubiquitination	up-regulates activity	0.2	As a result, knockdown of RNF26 promoted degradation of MITA after viral infection and prevented degradation of IRF3.\|In addition, RNF26 could not induce polyubiquitination of MITA (K150R) in in vitro ubiquitination assays (XREF_FIG).	SIGNOR-278573

P07550

O95837

2

binding

up-regulates activity

0.314

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-257192

Q16236

P05771

0

phosphorylation

up-regulates

0.418

Phosphorylation of nrf2 at ser-40 by protein kinase c regulates antioxidant response element-mediated transcription / recently we reported evidence for the involvement of protein kinase c (pkc) in phosphorylating nrf2 and triggering its nuclear translocation in response to oxidative stress

SIGNOR-91830

Q00987

O15151

2

ubiquitination

down-regulates

0.733

The mdm2 homolog mdmx is an important regulator of p53 during mouse embryonic development. Dna damage promotes mdmx phosphorylation, nuclear translocation, and degradation by mdm2.

SIGNOR-144970

P68400

Q13829

1

phosphorylation

up-regulates

0.2

It was demonstrated that ck2 could phosphorylate tnfaip1 in vitro and in vivo, which facilitated the distribution of tnfaip1 in nucleus and enhanced its interaction with pcna. It is suggested that the phosphorylation of tnfaip1 may be required for its functions.

SIGNOR-188849

O75116

O14950

1

phosphorylation

up-regulates activity

0.598

In addition, an in vitro kinase assay with mixed recombinant GST-ROCK2 and MLC2 revealed that ROCK2 phosphorylated WT MLC2, but not MLC2 S15A mutant, indicating that it phosphorylates MLC2 at S15 in vitro (XREF_FIG).

SIGNOR-279103

Q13362

O96017

0

phosphorylation

up-regulates

0.322

Found that chk2 associated with the b' regulatory subunit of protein phosphatase pp2a. In vitro kinase assays showed that b'gamma3 was a potent chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of pp2a.

SIGNOR-129255

Q9NZN5

Q05397

0

phosphorylation

up-regulates activity

0.303

These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa.

SIGNOR-279310

Q16665

P15692

1

transcriptional regulation

up-regulates quantity

0.773

Transcription of the human erythropoietin (EPO) gene is activated in Hep3B cells exposed to hypoxia. Hypoxia-inducible factor 1 (HIF-1) is a nuclear factor whose DNA binding activity is induced by hypoxia in Hep3B cells, and HIF-1 binds at a site in the EPO gene enhancer that is required for hypoxic activation of transcription.

SIGNOR-256592

P42574

P09874

1

cleavage

down-regulates activity

0.775

Caspase-3 cleaves parp-1. During cd95-mediated apoptosis proteolytic inactivation of parp-1 by caspases prevents atp depletion and thereby ensures the execution of the apoptotic process

SIGNOR-116178

P29353

P14784

2

binding

up-regulates

0.558

The signaling mechanism utilizes an adaptor protein, shc, which binds to a phosphotyrosine residue on the il-2/15r?, Resulting in activation of grb2 and onto akt via the shc-grb2-gab2-pi3k-akt signaling pathway to increase cell proliferation and/or survival

SIGNOR-204975

P32238

P30679

2

binding

up-regulates activity

0.485

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-257410

Q8TAF3

O94782

2

binding

up-regulates activity

0.946

In vitro reconstitution of USP1 deubiquitinating enzyme activity, using either ubiquitin-7-amido-4-methylcoumarin (Ub-AMC) or purified monoubiquitinated FANCD2 protein as substrates, demonstrates that UAF1 functions as an activator of USP1. UAF1 binding increases the catalytic turnover (kcat) but does not increase the affinity of the USP1 enzyme for the substrate (KM).

SIGNOR-263274

P22681

Q9BX66

2

binding

up-regulates

0.688

Cbl is recruited to the insulin receptor by interaction with the adapter protein cap, through one of three adjacent sh3 domains in the carboxy terminus of cap

SIGNOR-82283

O95198

Q9BYP7

2

binding

down-regulates quantity by destabilization

0.476

We found that KLHL2, as well as KLHL3, was co-immunoprecipitated with all four WNK isoforms. The direct interaction of KLHL2 with WNKs was confirmed on fluorescence correlation spectroscopy. Co-expression of KLHL2 and Cullin3 decreased the abundance of WNK1, WNK3 and WNK4 within HEK293T cells, and a significant increase of WNK4 ubiquitination by KLHL2 and Cullin3 was observed both in HEK293T cells and in an in vitro ubiquitination assay. These results suggest that KLHL2-Cullin3 also functions as an E3-ligase for WNK isoforms within the body.

SIGNOR-272121

O60641

P63027

2

binding

up-regulates quantity

0.63

the monomeric adaptor proteins AP180/CALM and stonin-2 are required for the efficient retrieval of synaptobrevin II (sybII) and synaptotagmin-1 respectively. Furthermore, recent studies have revealed that sybII and synaptotagmin-1 interact with other SV cargoes to ensure a high fidelity of retrieval.

SIGNOR-264112

P41091

Q9UI10

0

guanine nucleotide exchange factor

up-regulates activity

0.698

EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.

SIGNOR-269137

P31269

O43189

0

transcriptional regulation

down-regulates quantity by repression

0.286

These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.

SIGNOR-260069

P42229

Q9NSE2

1

transcriptional regulation

up-regulates quantity by expression

0.669

The STAT5 target gene CIS, a member of the suppressor of cytokine signaling (SOCS) protein family, was highly induced by Flt3-ITD

SIGNOR-261544

P35712

Q14669

0

ubiquitination

down-regulates quantity by destabilization

0.397

In this article, we focused on Trip 12, an E3 ubiquitin ligase, which polyubiquitinates Sox6.|Therefore, Sox6 is a specific substrate to Trip12, by which it is polyubiquitinated and degraded.

SIGNOR-278579

P35968

P12931

0

phosphorylation

up-regulates activity

0.614

In contrast, our analysis showed that over-expression of c-Src significantly enhances the ability of VEGFR-2 to stimulate proliferation of PAE cells and over-expression of dominant negative Src (Src kinase-dead) inhibits the VEGFR-2 driven proliferation of PAE cells (XREF_FIG).|Taken together, the data demonstrate that Src kinases upon activation by VEGFR-2 phosphorylate Y1173 of VEGFR-2 (XREF_FIG).

SIGNOR-279120

Q99081

Q02535

2

binding

down-regulates activity

0.466

All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo.

SIGNOR-241152

P06730

P17252

0

phosphorylation

up-regulates

0.382

Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .

SIGNOR-248945

P10586

Q13136

0

relocalization

up-regulates activity

0.8

We have identified a novel cytoplasmic 160 kDa phosphoserine protein termed LAR-interacting protein 1 (LIP.1), which binds to the LAR membrane-distal D2 protein tyrosine phosphatase domain and appears to localize LAR to focal adhesions.

SIGNOR-264141

P32121

P07550

2

binding

down-regulates activity

0.724

The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors

SIGNOR-256501

P12830

Q9UQB3

2

binding

up-regulates quantity by stabilization

0.447

To clarify the role of p120 in mammalian cells, we have knocked down p120 with siRNA in cells expressing epithelial (E-), placental (P-), neuronal (N-), and vascular endothelial (VE-) cadherins. We report that each of these cadherins, as well as α- and β-catenins, were rapidly degraded in the absence of p120, resulting in loss of cell–cell adhesion. The effect was clearly dose dependent, indicating that p120 expression levels may directly determine cadherin levels. Degradation of p120-uncoupled cadherin occurred after its arrival at the surface, indicating that p120 regulates cadherin turnover at the level of internalization or recycling. p120 homologues ARVCF and δ-catenin could substitute for p120, so at least one family member is likely required to maintain adhesion. Thus, cadherin complexes are rapidly turned over and degraded in mammalian cells in the absence of direct interaction with p120 or a p120 family member.

SIGNOR-252134

Q05209

O43586

1

dephosphorylation

down-regulates activity

0.61

We also demonstrate that PTP-PEST dephosphorylates PSTPIP at tyrosine 344. Importantly, we identified tyrosine 344 as the main phosphorylation site of PSTPIP by performing tryptic phosphopeptide maps. |The biological functions of the complexes formed between PSTPIP and SH2 domain-containing tyrosine kinases may be to transmit the signals from activated EGF and PDGF receptor.|Furthermore, we show that PSTPIP is phosphorylated downstream of the activated PDGF and EGF receptors. This phosphorylation of PSTPIP is most likely mediated by c-Abl

SIGNOR-248656

Q8NHZ8

O95835

0

phosphorylation

up-regulates activity

0.466

LATS1 and LATS2 phosphorylate CDC26 to modulate assembly of the tetratricopeptide repeat subcomplex of APC/C|Overall, these results suggest that LATS1/2 are novel kinases involved in APC/C phosphorylation and indicate a direct regulatory link between LATS1/2 and APC/C|Here, we demonstrate that LATS1 phosphorylates the Thr7 (T7) residue of the APC/C component CDC26 directly

SIGNOR-275472

O15105

P84022

1

transcriptional regulation

down-regulates quantity

0.613

The downstream molecules including mad2, smad3, smad4 and smad7 are involved in TGF-β1-induced EMT,while Smad7 blocks the smad3 expression

SIGNOR-260437

Q5TZA2

P24941

0

phosphorylation

down-regulates

0.2

Finally, phosphorylation of tax1bp2 at serine-763 by cyclin-dependent kinase (cdk)2 abolished the tax1bp2-mediated p38 activation and tumor-suppressive activity, indicating that tax1bp2 can adapt cdk2 signaling to the p38/p53/p21 pathway.

SIGNOR-197593

Q15418

P49815

1

phosphorylation

down-regulates

0.768

The mitogen-activated protein kinase (mapk)-activated kinase, p90 ribosomal s6 kinase (rsk) 1, was found to interact with and phosphorylate tuberin at a regulatory site, ser-1798, located at the evolutionarily conserved c terminus of tuberin. Rsk1 phosphorylation of ser-1798 inhibits the tumor suppressor function of the tuberin/hamartin complex, resulting in increased mtor signaling to s6k1

SIGNOR-128634

P84550

P52954

2

binding

down-regulates activity

0.558

Furthermore, Corl1 interacted with Lbx1 and cooperatively repressed transcription, suggesting that it acts as a transcriptional corepressor for Lbx1 in regulating cell fate determination in the dorsal spinal cord.

SIGNOR-238004

P15056

P36507

1

phosphorylation

up-regulates

0.75

We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l.

SIGNOR-42664

Q9UPT5

P28482

0

phosphorylation

up-regulates

0.331

Erk1/2 phosphorylation enhances the binding of exo70 to other exocyst components and promotes the assembly of the exocyst complex in response to epidermal growth factor (egf) signaling.

SIGNOR-197543

Q9ULU4

P03956

1

transcriptional regulation

down-regulates quantity by repression

0.2

Our quantitative ChIP experiments confirmed that ZMYND8 and JARID1D were co-localized at Slug, CD44, VEGFA, and EGFR genes (Figures 4F–4I). Our ChIP results also showed that ZMYND8 repressed and occupied other JARID1D target genes, such as the matrix metalloproteinase 1 (MMP1) and MMP3, that we previously reported

SIGNOR-262042

P05787

P06493

0

phosphorylation

up-regulates

0.248

With regard to k8 phosphorylation at ser-431, it increases dramatically upon stimulation of cells with epidermal growth factor (egf) or after mitotic arrest and is the major k8 phosphorylated residue after incubating k8 immunoprecipitates with mitogen-activated protein or cdc2 kinases.

SIGNOR-56054

Q99683

O75460

1

phosphorylation

up-regulates activity

0.618

ASK1 may directly phosphorylate IRE1\u03b1 at sites other than the IRE1\u03b1 autophosphorylation site.

SIGNOR-279213

P33991

Q13535

0

phosphorylation

up-regulates

0.724

Together these data strongly support the conclusion that mec1 directly targets the s/tq sites in mcm4 and mcm6, although it is formally possible that mec1 and mrc1 activate a different s/tq-directed kinase to target mcm4 and mcm6.

SIGNOR-169412

Q05655

P51398

1

phosphorylation

up-regulates

0.2

Dap3 is phosphorylated by protein kinase cdelta on thr237. Dap3 was originally identified as a pro-apoptotic protein. The mutation of the phosphorylation site thr237 to alanine reversed the cell death caused by the wild-type dap3

SIGNOR-160488

P17612

Q9Y698

1

phosphorylation

down-regulates activity

0.432

phosphorylation of stargazin at T321 by PKA inhibits its interaction with PSD-95.

SIGNOR-250342

Q13635

O94991

2

binding

down-regulates activity

0.2

SLITRK5 interacts with SHH and PTCH1. Mechanistically, SLITRK5 binds to hedgehog ligands via its extracellular domain and interacts with PTCH1 via its intracellular domain. SLITRK5 is present in the primary cilium, and loss of SLITRK5 enhances SMO ciliary enrichment upon SHH stimulation. Thus, SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts that may be attractive as a therapeutic target to enhance bone formation.

SIGNOR-268438

P23467

P08581

1

dephosphorylation

down-regulates

0.364

Ptp1b and shp-2 are bound to the c-met receptor to control its activity. Although the binding of ptp1b increases when there is a decrease in c-met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of shp-2 coincide with maximal stimulation of c-met, acting as a positive regulator.

SIGNOR-139560

P42681

P06241

0

phosphorylation

up-regulates activity

0.347

We further demonstrate that Rlk can be phosphorylated and activated by Src kinases, leading to a decrease in its half-life. A specific tyrosine in the activation loop of Rlk, Y420, is required for phosphorylation and activation, as well as for decreased stability, but is not required for lipid RAFT association.

SIGNOR-249341

P25025

P42830

2

binding

up-regulates activity

0.752

CXCL5 is another ELR+ CXC chemokine and, thus, also potently attracts neutrophils. Just like CXCL1, CXCL5 also signals through CXCR2, explaining why, often, CXCL5 and CXCL1 are seen to function in parallel in PDAC. CXCL5 was increased in human pancreatic tissue compared to the normal pancreas, and the knockdown of CXCL5 in pancreatic cancer cell lines reduced the proliferation and migration ability of cells

SIGNOR-277730

Q15418

P30305

1

phosphorylation

up-regulates

0.253

Rsk promotes g2/m transition through activating phosphorylation of cdc25a and cdc25b rsk is likely to be more active in mitotic cells than in interphase cells, as evidenced by the phosphorylation status of t359/s363 in rsk. Together, these findings indicate that rsk promotes g2/m transition in mammalian cells through activating phosphorylation of cdc25a and cdc25b.

SIGNOR-202125

Q2TAL8

O95363

1

transcriptional regulation

up-regulates quantity by expression

0.2

QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.

SIGNOR-269403

Q13635

P42574

0

cleavage

down-regulates

0.321

Like other dependence receptors, ptc1 contains a dependence-as-associated receptor c-terminal motif that is cleaved by caspases at a conserved aspartic acid (asp 1392) in the absence of shh, to expose a proapoptotic domain.

SIGNOR-199111

Q8TDC3

P30307

1

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

Q13153

2

phosphorylation

up-regulates activity

0.2

Cdc42 and Rac1 cause alpha-PAK autophosphorylation and kinase activation.

SIGNOR-250219

Q9UPZ9

Q8N122

1

phosphorylation

up-regulates

0.2

Our findings demonstrate an important role for ick in modulating the activity of mtorc1 through phosphorylation of raptor thr-908 and thus implicate a potential signaling mechanism by which ick regulates cell proliferation and division.

SIGNOR-196198

P68400

P08575

1

phosphorylation

up-regulates

0.442

Mutational analysis of ck2 consensus sites showed that the target for ck2 was in an acidic insert of 19 amino acids in the d2 domain, and ser to ala mutations at amino acids 965, 968, 969, and 973 abrogated ck2 phosphorylation of cd45. Ck2 phosphorylation increased cd45 activity 3-fold toward phosphorylated myelin basic protein,

SIGNOR-65277

O00533

Q12955

1

relocalization

up-regulates quantity

0.412

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266723

P28482

Q969V6

1

phosphorylation

down-regulates

0.2

Serum induces rhoa-dependent translocation of mkl1 from the cytoplasm to the nucleus and also causes a rapid increase in mkl1 phosphorylation. Serum-induced phosphorylation of the serum response factor coactivator mkl1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization.

SIGNOR-195153

Q9Y5I2

Q9Y5G0

2

binding

up-regulates activity

0.2

The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.

SIGNOR-265714

Q9UQL6

P17612

0

phosphorylation

up-regulates activity

0.2

PKA/Cdk5-mediated phosphorylation of HDAC5 at Ser279 within the NLS promotes nuclear localization of HDAC5 and interaction with the nuclear corepressor complex

SIGNOR-198658

P45983

Q16828

0

dephosphorylation

down-regulates activity

0.632

Our data demonstrate MKP-3 has differential substrate preference in astrocytes compared to other cells types, since it preferentially dephosphorylated p-JNK over p-ERK.|The main findings of our studies are (1) MKP-3 preferentially reduces p-JNK over p-ERK and p-p38 in primary astrocytes; (2) This MAPK modulation pattern in primary astrocytes significantly reduced NO and completely abolished IL-6 and TNF accumulation; and (3) These effects are specifically induced by MKP-3 since block-age of MKP-3 mRNA expression reversed its action on MAPKs and pro-inflammatory mediators in BV-2 microglia cells.

SIGNOR-277150

P17252

Q13769

1

phosphorylation

up-regulates

0.327

We conclude m-csf-mediated activation of pkcalpha can potentiate fmip action to initiate survival/differentiation signaling.

SIGNOR-126572

O00418

Q13131

0

phosphorylation

down-regulates activity

0.492

AMPK can phosphorylate three sites in eEF2 kinase in vitro. Of these, Ser-398 appears to be more efficiently phosphorylated than either Ser-78 or Ser-366. Ser-78 and Ser-366 do not appear to be phosphorylated by AMPK within cells. Ser-366 serves to decrease the activity of eEF2 kinase

SIGNOR-250314

Q06187

Q03113

2

binding

up-regulates activity

0.317

Here we show that Ga12 binds directly to, and stimulates the activity of, Bruton’s tyrosine kinase (Btk) and a Ras GTPase-activating protein, Gap1m, in vitro and in vivo

SIGNOR-278082

Q70YC5

P09874

2

binding

up-regulates activity

0.2

We identified ZNF365 as a necessary component of the HR repair pathway. ZNF365 interacts with PARP1 and tethers MRE11 to the nucleolytic resection sites for replication fork recovery

SIGNOR-272477

Q16539

P49137

1

phosphorylation

up-regulates activity

0.769

Here we show that in vitro rk phosphorylates human gst-mapkap kinase-2 at thr25 in the proline-rich n-terminal region thr222 and ser272 in the catalytic domain and thr334 in the c-terminal domain. Using novel methodology we demonstrate that activation of mapkap kinase-2 requires the phosphorylation

SIGNOR-44351

P51955

P35222

1

phosphorylation

down-regulates quantity

0.469

NEK2 silencing reduced the phosphorylation of beta-catenin at Ser33 and Ser37, but did not decrease the level of total beta-catenin.|NEK2 slightly decreased the level of total beta-catenin (XREF_FIG).

SIGNOR-278173

P12931

P52757

1

phosphorylation

down-regulates

0.2

Here we report that beta2-chimaerin is tyrosine-phosphorylated by src-family kinases (sfks) upon cell stimulation with epidermal growth factor (egf). Mutational analysis identified tyr-21 in the n-terminal regulatory region as a major phosphorylation site. these results suggest tyr-21 phosphorylation as a novel, sfk-dependent mechanism that negatively regulates beta2-chimaerin rac-gap activity.

SIGNOR-155713

O00744

Q13467

2

binding

up-regulates

0.619

Inhibition of adipogenesis by wnt10b is likely mediated by‚ wnt‚ receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 8

SIGNOR-210164

Q9UBP0

P53990

0

relocalization

up-regulates activity

0.519

Our results suggest that inclusion of IST1 into the ESCRT complex allows recruitment of spastin to promote fission of recycling tubules from the endosome. Thus, we reveal a novel cellular role for MT severing and identify a mechanism by which endosomal recycling can be coordinated with the degradative machinery.

SIGNOR-269047

P12318

P06241

0

phosphorylation

up-regulates activity

0.534

To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and point|Fyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation.

SIGNOR-249336

P63096

P28221

2

binding

up-regulates activity

0.435

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-256721

P49715

P49675

1

transcriptional regulation

up-regulates quantity by expression

0.335

Electrophoretic mobility shift assay demonstrated that this region of the StAR promoter was bound by C/EBPalpha, C/EBPbeta, and CREB. Forced expression of either C/EBPalpha or C/EBPbeta alone was sufficient to up-regulate StAR promoter activity whereas PGE(2) was needed to induce StAR promoter activity in CREB-overexpressed cells.

SIGNOR-254043

Q9GZV5

Q9NRM7

0

phosphorylation

down-regulates

0.698

Activated lats1/2 in turn phosphorylate and inhibit yap/taz transcription co-activators

SIGNOR-175787

P54753

Q15768

2

binding

up-regulates

0.821

Ephrin-b3, a ligand for the receptor ephb3, expressed at the midline of the developing neural tube.

SIGNOR-54711

P07550

P38405

2

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

P03951

P00748

0

cleavage

up-regulates activity

0.494

Activation of factor XI in plasma is dependent on factor XII | Similar kinetics of factor XI cleavage are seen when 40 nmol/L factor XIIa (equal to 10% of factor XII activation) is added to factor XII-deficient plasma if an activating surface is provided.

SIGNOR-263519

Q7L2J0

Q6NYC1

0

cleavage

down-regulates activity

0.268

JMJD6 cleaves MePCE. we propose that JMJD6 is the cognate protease of MePCE and cleaves at the R171 site within MePCE. Experiments using purified JMJD6 showed that it could make a cut in an enzyme called MePCE, which belongs to the group of proteins that hold P-TEFb in its inactive form. The levels of activated Pol II were lower in cells without JMJD6 and higher in those without MePCE. Together, the results suggest that JMJD6 cuts MePCE to release P-TEFb, which then activates Pol II.

SIGNOR-261037

Q96BR1

Q86YD1

1

phosphorylation

down-regulates quantity by destabilization

0.2

In this study, we find that the understudied serum and glucocorticoid-induced kinase-2 (SGK2) phosphorylates PTOV1 at S36.

SIGNOR-279283

P19484

Q9GZQ8

1

transcriptional regulation

up-regulates quantity by expression

0.391

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276559

Q99706

P17693

2

binding

up-regulates

0.764

Recombinant soluble kir2dl4 binds to cells expressing hla-g but not to cells expressing other hla class i molecules.

SIGNOR-66132

P40763

P43378

0

dephosphorylation

down-regulates activity

0.432

Results are presented as mean \u00b1 SD from three independent experiments. (B) PTPMeg2 inhibits STAT3-mediated transcriptional activity in a dose dependent manner.|These results indicate that PTPMeg2 inhibits STAT3 activation with certain specificity.|In this study, we demonstrated that PTPMeg2 dephosphorylates STAT3 at the Tyr705 residue by a direct interaction.

SIGNOR-276976

Q9UNE7

Q86WG3

1

polyubiquitination

down-regulates quantity by destabilization

0.378

CHIP e.g. was found to efficiently polyubiquitinate caytaxin in vitro, suggesting that it might influence caytaxin degradation in vivo.

SIGNOR-272651

Q9BV47

Q13158

1

dephosphorylation

down-regulates activity

0.366

This multi-functionality of fadd may depend primarily on its subcellular location. Fadd shuttles between the cytosol and the nucleus and this signal is unclear;however, fadd trafficking requires phosphorylation of the protein on ser194dusp26 suppresses cell proliferation by fadd dephosphorylation

SIGNOR-204559

P29474

Q14289

0

phosphorylation

down-regulates

0.309

We found that fluid shear stress induces the association of enos with the proline-rich tyrosine kinase 2 (pyk2) in endothelial cells and that the enos immunoprecipitated from enos- and pyk2-overexpressing hek293 cells was tyrosine-phosphorylated on tyr657.

SIGNOR-161824

O60216

P04114

1

transcriptional regulation

down-regulates quantity

0.2

The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector.

SIGNOR-259974

P49841

P11388

1

phosphorylation

down-regulates quantity by destabilization

0.348

This study also reports the novel finding that topoIIα may be a target of GSK3β phosphorylation. Evidence suggests that CK2 serves as a priming kinase, through phosphorylation at Ser1365, for GSK3β-mediated phosphorylation at Ser1361.

SIGNOR-276301

P14653

P40424

2

binding

up-regulates activity

0.807

Pbx1 and exd act as cofactors that enhance the DNA binding specificity of Hox proteins. The structure of the HoxB1Pbx1DNA ternary complex shows that HoxB1 and Pbx1 bind to overlapping binding sites located on opposite faces of the DNA.

SIGNOR-241219

P06493

P18031

1

phosphorylation

up-regulates activity

0.502

Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.

SIGNOR-272970

P24941

P26358

1

phosphorylation

up-regulates

0.342

We report that cyclin-dependent kinases (cdks) 1, 2 and 5 can phosphorylate ser154 of human dnmt1 in vitro. Further evidence of phosphorylation of endogenous dnmt1 at position 154 by cdks is also found in 293 cells treated with roscovitine, a specific inhibitor of cdk1, 2 and 5

SIGNOR-173681

P04406

Q13043

0

phosphorylation

up-regulates activity

0.279

Interestingly, GAPDH is phosphorylated by Mst1 to a comparable extent as its known substrate MBP, suggesting that GAPDH is a good substrate of Mst1 at least in vitro.|Moreover, interaction of Mst1 with GAPDH caused a robust phosphorylation of GAPDH and markedly increased the Mst1 activity in cells.

SIGNOR-279295

P25963

Q04206

2

binding

up-regulates activity

0.891

Nf-kappa b is an inducible transcription factor comprised of a 50-kd (p50) and a 65-kd (p65) subunit. Induction of nf-kappa b activity, which is a critical event in many signal transduction pathways, involves release from a cytoplasmic inhibitory protein, i kappa b, followed by translocation of the active transcription factor complex into the nucleus. we demonstrate by in vitro and in vivo methods that the recently cloned i kappa b/mad-3 interacts with both the p50 and p65 subunits of nf-kappa b.

SIGNOR-17691

O75582

P19419

1

phosphorylation

up-regulates

0.2

Phosphorylation on ser383 and ser389 of elk-1 by mapk enhances this basal binding but, most importantly, elk-1 exhibits new interactions with p300.

SIGNOR-85514

P55211

O15392

2

binding

down-regulates

0.504

Survivin (an inhibitor of apoptosis) phosphorylation on thr34 may regulate apoptosis at cell division via an interaction with caspase-9.

SIGNOR-84065

O00141

Q13164

0

phosphorylation

up-regulates

0.388

Bmk1 mediates growth factor-induced cell proliferation through direct cellular activation of serum and glucocorticoid-inducible kinasebmk1 activates sgk by phosphorylation at serine 78.

SIGNOR-105728

Q96BK5

P53350

0

phosphorylation

down-regulates

0.361

Here, we show that polo-like kinase 1 (plk1) is a novel interacting protein of pinx1. Plk1 interacts with and phosphorylates pinx1 in vivo and in vitro. Moreover, plk1-mediated phosphorylation of pinx1 at five phosphorylation sites is essential for its plk1-induced degradation.

SIGNOR-166333

Q9UH17

P17612

0

phosphorylation

down-regulates activity

0.2

Here we show that protein kinase A (PKA) physically binds to A3B and phosphorylates Thr214.

SIGNOR-277455

P31276

P55268

1

transcriptional regulation

up-regulates quantity by expression

0.2

The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interaction of these homeoproteins with the origin sequence in mammalian cells.

SIGNOR-261644

Q8IWU2

P13569

1

phosphorylation

down-regulates activity

0.401

The present study discovered that in human airway epithelial cells CFTR endocytosis is regulated by the LMTK2-mediated phosphorylation of CFTR-Ser737 that decreases the cell surface density of CFTR Cl\u2212 channels and inhibits CFTR-mediated Cl\u2212 secretion.|Together, the above results demonstrate that the LMTK2 phosphorylation of CFTR-Ser737 facilitates CFTR endocytosis and reduces the plasma membrane abundance of CFTR in human airway epithelial cells.

SIGNOR-278227

P09211

P17252

0

phosphorylation

up-regulates activity

0.2

Peptide phosphorylation analyses and both phosphorylation and enzyme kinetic studies with GSTP1 proteins mutated at candidate amino acid residues established Ser-42 and Ser-184 as putative phospho-acceptor residues for both kinases in the GSTP1 protein. Together, these findings show PKA- and PKC-dependent phosphorylation as a significant post-translational mechanism of regulation of GSTP1 function. Together, these results further support S42 and S184 as major phosphor-acceptor residues for PKA and PKC and suggest that the increased activity of the phospho-GSTP1 was not simply a consequence of the negative charge introduced in the GSTP1 protein by the phosphate group.All eight PKC isoforms, PKC-α, PKC-βI, PKC-βII, PKC-ε, PKC-γ, PKC-η, and PKC-ζ phosphorylated the GSTP1 protein efficiently

SIGNOR-276024

P06241

Q9UQC2

1

phosphorylation

up-regulates activity

0.605

Our studies show that Gab2 is activated by Fyn kinase upon the engagement of ligand to TNFR1, IL-1R, or TLR4.|TNF\u03b1, IL-1\u03b2, and LPS induce Fyn kinase-mediated phosphorylation of Gab2.

SIGNOR-279984

P24385

P03372

0

transcriptional regulation

up-regulates quantity by expression

0.754

Ikkalpha in conjunction with eralpha and aib1/src-3, is important in activating the transcription of estrogen-responsive genes, including cyclin d1.

SIGNOR-135053

P49674

Q92997

2

phosphorylation

down-regulates activity

0.669

Co-expression of CK1ϵ with FLAG-Dvl3 retards electrophoretic migration and induces phosphorylation-dependent shift of Dvl (PS-Dvl3). mutations of Ser-280 and Ser-311 prevent efficient activation of Wnt/β-catenin by Dvl3.

SIGNOR-276645

Q8N2W9

P42224

2

binding

down-regulates

0.561

First, piasy interacts with stat1 both in vitro and in vivo. The in vivo piasy__stat1 interaction is dependent on cytokine stimulation. Second, piasy can inhibit stat1-mediated gene activation without blocking the dna binding activity of stat1.

SIGNOR-105723

Q02388

P13497

0

cleavage

up-regulates quantity

0.604

We show that bone morphogenetic protein-1 (BMP-1), which exhibits procollagen C-proteinase activity, cleaves the C-terminal propeptide from human procollagen VII. The cleavage occurs at the BMP-1 consensus cleavage site SYAA/DTAG within the NC-2 domain. Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen.

SIGNOR-256338

Q9BY78

Q86WV6

1

ubiquitination

up-regulates activity

0.2

As a result, knockdown of RNF26 promoted degradation of MITA after viral infection and prevented degradation of IRF3.|In addition, RNF26 could not induce polyubiquitination of MITA (K150R) in in vitro ubiquitination assays (XREF_FIG).

SIGNOR-278573