GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P17252	Q15672	1	phosphorylation	up-regulates quantity by stabilization	0.2	Because most of these sites were predicted to be phosphorylated by protein kinase C (PKC), we overexpressed PKCα in several cell lines and found that it phosphorylates Twist1 on Ser-144. we observed that PKCα-mediated Twist1 phosphorylation at Ser-144 inhibits Twist1 ubiquitination and consequently stabilizes it.	SIGNOR-277429
P57078	O14641	1	phosphorylation	up-regulates activity	0.44	Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.\|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling.	SIGNOR-279756
Q9ULH1	Q14289	0	phosphorylation	down-regulates activity	0.458	The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. Pyk2 directly phosphorylates ASAP1 on tyrosine residues in vitro and increases ASAP1 tyrosine phosphorylation when co-expressed in HEK293T cells.Phosphorylation of tyrosine 308 and 782 affects the phosphoinositide binding profile of ASAP1, and fluorimetric Arf-GTPase assays with purified proteins revealed an inhibition of ASAP1 GTPase-activating protein activity by Pyk2-mediated tyrosine phosphorylation.	SIGNOR-263186
P17252	P38936	1	phosphorylation	up-regulates activity	0.375	Binding of calmodulin to the carboxy-terminal region of p21 induces nuclear accumulation via inhibition of protein kinase c-mediated phosphorylation of ser153\| When phosphorylated at Ser153, p21 is located at the cytoplasm and disrupts stress fibers.	SIGNOR-139302
Q99466	Q00987	0	ubiquitination	down-regulates	0.37	We demonstrate that the intracellular domain of notch 4 is targeted for ubiquitylation and hence degradation by the ubiquitin ligase mdm2.	SIGNOR-172826
P09619	P22681	0	polyubiquitination	down-regulates quantity by destabilization	0.629	Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha.	SIGNOR-272549
P45983	P22736	1	phosphorylation	down-regulates	0.5	We also identified the exact phosphorylation site of jnk to be serine 95 at the n terminus of tr3, around which a classical jnk phosphorylation motif exists. Furthermore, we demonstrated that tr3 phosphorylation by jnk coincided with its ubiquitination and degradation, resulting in the loss of its mitogenic activity.	SIGNOR-149998
P68400	O43156	1	phosphorylation	down-regulates	0.2	Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1	SIGNOR-200240
Q8NFU7	O94813	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259093
Q92835	P16885	1	dephosphorylation	down-regulates activity	0.312	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268455
P31749	P49815	1	phosphorylation	down-regulates activity	0.817	We demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites for PI3K-dependent S/T kinases. Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo. We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN(-/-) tumor-derived cell lines.	SIGNOR-235515
O75582	P0C0S8	1	phosphorylation	up-regulates	0.2	We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.	SIGNOR-123383
P27361	Q9UQC2	1	phosphorylation	up-regulates	0.617	Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623.	SIGNOR-128731
Q7L9L4	Q13043	0	phosphorylation	up-regulates	0.851	Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction.	SIGNOR-175841
P16104	P51812	0	phosphorylation	up-regulates activity	0.2	Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.\|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF.	SIGNOR-279349
P45985	Q9Y2U5	0	phosphorylation	up-regulates activity	0.612	Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation	SIGNOR-107695
Q13315	P04637	1	phosphorylation	up-regulates quantity by stabilization	0.843	In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.	SIGNOR-115348
P68400	P35221	1	phosphorylation	down-regulates	0.39	We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.	SIGNOR-161847
P10911	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.754	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-260556
P10275	P29320	0	phosphorylation	up-regulates activity	0.273	These data suggest that Etk may be able to phosphorylate AR at Y534 and Y551/552, and the interaction between the Etk SH2 domain and phosphorylated ARY551/552 may promote their association.\|This is supported by our observations that the association between Etk and AR is increased after castration and Etk induces tyrosine phosphorylation of AR, leading an increase in AR stability and transcriptional activity under androgen depleted conditions.	SIGNOR-279371
Q9H2X6	Q00987	1	phosphorylation	down-regulates activity	0.537	HIPK2 inhibits both MDM2 gene and protein by, respectively, p53-dependent and independent regulations.\|This p53-independent effect is likely mediated by HIPK2 catalytic activity and we found that HIPK2 phosphorylates MDM2 in vitro.	SIGNOR-279465
O00327	P20393	0	transcriptional regulation	down-regulates quantity by repression	0.671	In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267983
P16949	P06493	0	phosphorylation	up-regulates activity	0.641	null	SIGNOR-279803
P31749	P23769	1	phosphorylation	down-regulates	0.524	We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity	SIGNOR-135614
P24941	Q15910	1	phosphorylation	up-regulates activity	0.547	Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1.	SIGNOR-255656
Q16566	P29475	1	phosphorylation	down-regulates activity	0.357	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250713
P04637	O94953	1	transcriptional regulation	up-regulates quantity by expression	0.281	KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter.	SIGNOR-263729
P31749	P52789	1	phosphorylation	up-regulates activity	0.445	K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization	SIGNOR-259984
P32780	Q01094	1	phosphorylation	down-regulates quantity by destabilization	0.434	TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase. E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase.	SIGNOR-251260
O60260	P05067	1	ubiquitination	down-regulates quantity	0.2	Similarly, in transgenic AD mice models, lentiviral parkin expression ubiquitinates Abeta to reduce its intracellular levels while preventing plaque deposition, and this is associated with induction of beclin dependent autophagy .\|Thus, parkin reduces Abeta levels by enhancing both UPS- and autophagy dependent clearance of Abeta.	SIGNOR-278709
Q96E17	Q9UJD0	0	relocalization	up-regulates activity	0.26	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264380
P28482	P67809	1	phosphorylation	up-regulates activity	0.47	ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.	SIGNOR-279227
P06493	Q12834	1	phosphorylation	down-regulates activity	0.935	Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C.	SIGNOR-279321
P17252	Q6UVK1	1	phosphorylation	up-regulates activity	0.2	Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2 expressed in U251 cells are both blocked by mutation of Thr(2256), identifying this residue as a primary phosphorylation site. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is therefore a key step for initiating cell polarization and motility.	SIGNOR-263162
Q5QNW6	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265394
Q13131	O00418	1	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
Q15637	Q8TAS1	0	phosphorylation	up-regulates	0.406	Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.	SIGNOR-199797
P27361	Q9NRA0	1	phosphorylation	up-regulates	0.521	Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1	SIGNOR-153387
Q13188	P67775	0	dephosphorylation	down-regulates	0.693	Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201266
P45985	O43379	0	relocalization	up-regulates activity	0.2	In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis	SIGNOR-271715
P62256	P17542	0	transcriptional regulation	up-regulates quantity by expression	0.326	Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.\|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.	SIGNOR-269000
Q9UJU2	P68400	0	phosphorylation	up-regulates	0.303	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-23958
P11511	P01100	0	transcriptional regulation	up-regulates quantity by expression	0.346	We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.	SIGNOR-254879
Q05086	P48436	1	ubiquitination	down-regulates quantity by destabilization	0.261	We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes by E6-AP and degraded by proteasomes.	SIGNOR-272134
P17181	P29597	0	phosphorylation	up-regulates activity	0.91	We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH-2-dependent manner. Furthermore, only latent, non-phosphorylated STAT2 interacts with this phosphopeptide. When this phosphopeptide is introduced into permeabilized cells, the IFN alpha-dependent tyrosine phosphorylation of both STATs is blocked. Finally, mutant versions of IFNaR1, in which Tyr466 is changed to phenylalanine, can act in a dominant negative manner to inhibit phosphorylation of STAT2.	SIGNOR-246934
P35626	Q16581	1	phosphorylation	down-regulates activity	0.2	These findings suggest that in agonist-stimulated mast cells GRK2 and GRK3 may phosphorylate C3aR at the same or distinct sites to promote receptor desensitization.	SIGNOR-279781
Q14494	P49841	0	phosphorylation	down-regulates	0.4	Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (nrf1) and inhibits pro-survival function of nrf1	SIGNOR-193450
P63000	Q8WWN8	0	gtpase-activating protein	down-regulates activity	0.47	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-260456
Q9C0A6	P68431	1	methylation	up-regulates activity	0.2	SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.	SIGNOR-264620
Q9Y6Q9	Q16877	0	phosphorylation	up-regulates activity	0.326	PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output	SIGNOR-267269
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
O15550	O43248	1	transcriptional regulation	up-regulates quantity by expression	0.302	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260026
O14965	P57073	1	phosphorylation	up-regulates activity	0.2	Therefore, Aurora-A not only directly phosphorylates SOX8 but also promotes SOX8 transcription indirectly by regulating c-Myc protein.	SIGNOR-280189
P10636	P53778	0	phosphorylation	down-regulates activity	0.525	Phosphorylation of tau by SAPK3 and SAPK4 markedly reduced the ability of tau to promote microtubule assembly. SAPK3 (also called ERK6 and p38) and SAPK4 phosphorylate recombinant tau protein at multiple Ser/Thr-Pro sites that are hyperphosphorylated in PHF-tau, with SAPK4 and SAPK3 being the most effective.	SIGNOR-250087
Q13976	P41220	1	phosphorylation	up-regulates activity	0.68	Thus, PKGI-alpha binds to, phosphorylates and activates RGS-2, attenuating receptor-mediated vascular contraction.	SIGNOR-249241
Q14596	P49841	0	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
P17252	Q8NFA2	1	phosphorylation	up-regulates	0.2	Phosphorylation of thr341 allows noxo1 to sufficiently interact with noxa1, an interaction that participates in nox1 activation.	SIGNOR-202482
Q14978	P17612	0	phosphorylation	up-regulates	0.307	Here we demonstrate that protein kinase a (pka)-dependent phosphorylation of nopp140 at ser 627, together with c/ebpbeta, induces agp gene expression synergistically.	SIGNOR-91186
O14757	Q08050	1	phosphorylation	up-regulates activity	0.371	In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.	SIGNOR-280224
P01903	P48382	0	transcriptional regulation	up-regulates quantity by expression	0.503	In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. \| We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.	SIGNOR-266228
Q13131	Q9P1W9	0	phosphorylation	down-regulates activity	0.2	Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth.	SIGNOR-277471
Q13085	P54646	0	phosphorylation	down-regulates	0.697	Significant negative linear correlations between phospho-acc and acc activity were observed in all models (p < 0.01). The decline in acc activity was related to the decrease in pcr and the rise in amp. A relationship between phospho-ampk (threonine 172) and activity of ampk immunoprecipitated with anti-alpha(2) subunit antibody preparation was also observed.	SIGNOR-87583
P05106	P31749	0	phosphorylation	down-regulates activity	0.613	A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules.	SIGNOR-252552
Q96LC7	P06239	0	phosphorylation	up-regulates	0.26	These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling	SIGNOR-112491
P42226	P23458	0	phosphorylation	up-regulates activity	0.765	IL-4-stimulated Stat6 activation is mediated by Jak1 whereas Tyk2 is required for Stat6 activation in IL-13-treated monocytes	SIGNOR-249531
O94763	P23443	0	phosphorylation	down-regulates activity	0.344	Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.	SIGNOR-262943
P35222	P18031	0	dephosphorylation	up-regulates activity	0.66	PTP1B modulates the association of beta-catenin with N-cadherin through binding to an adjacent and partially overlapping target site.\|The nonreceptor tyrosine phosphatase PTP1B associates with the cytoplasmic domain of N-cadherin and may regulate cadherin function through dephosphorylation of beta-catenin.\|Thus, interaction of PTP1B with N-cadherin is essential for its association with beta-catenin, stable expression at the cell surface, and consequently, cadherin function.	SIGNOR-277121
Q86YT6	P54132	1	ubiquitination	down-regulates quantity by destabilization	0.281	BLM is Ubiquitinated by E3 Ligase MIB1.\|Moreover, MIB1 mediated BLM degradation in G1 phase appears to be important for DNA double-strand break repair.	SIGNOR-278548
Q96EB6	O43524	1	deacetylation	up-regulates activity	0.911	Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress	SIGNOR-122405
P00519	P53350	1	phosphorylation	up-regulates activity	0.29	C-ABL can directly phosphorylate PLK1 and activate PLK1. \| The above results indicate that c-ABL–mediated PLK1 Y425 phosphorylation regulates PLK1 ubiquitination and stability.	SIGNOR-260935
P00519	P40763	1	phosphorylation	up-regulates activity	0.445	Previously, we showed that c-Abl and Arg promote phosphorylation of the STAT3 transcription factor (Y705) in a variety of cancer cell lines , .\|Since c-Abl and Arg activate STAT3, we investigated whether c-Abl and Arg regulate NF-kappaB signaling.	SIGNOR-279675
Q16539	Q16644	1	phosphorylation	up-regulates activity	0.714	These results, taken together, suggest the importance of the docking interaction in the efficient phosphorylation and activation of 3pk by p38.	SIGNOR-235451
Q00536	O43663	1	phosphorylation	up-regulates activity	0.344	Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.\|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process	SIGNOR-273017
P51812	Q96RK0	1	phosphorylation	down-regulates	0.2	Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)	SIGNOR-169887
O75628	Q15139	0	phosphorylation	up-regulates activity	0.356	We found that activation of protein kinase D1, a protein kinase downstream of α(1)-adrenergic signaling, leads to direct phosphorylation of Rem1 at Ser18. This results in an increase of the channel activity and plasma membrane expression observed by using a combination of electrophysiology, live cell confocal microscopy, and immunohistochemistry in heterologous expression system and neonatal cardiomyocytes.	SIGNOR-273832
Q9H2X6	P12931	0	phosphorylation	up-regulates activity	0.307	Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.\|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.	SIGNOR-278989
Q14258	P11308	1	ubiquitination	down-regulates quantity	0.301	We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG.\|Our previous discovery of USP9X as an ERG stabilizing deubiquitinase suggests that reduction of ERG protein levels by TRIM25 mediated proteasomal degradation is prevented by expression of USP9X in fusion positive prostate cancer cells.\|Using several biochemical assays we show that TRIM25 mediates the polyubiquitination of full-length ERG as well as N-terminally truncated ERG.	SIGNOR-278732
P11308	P56704	1	transcriptional regulation	up-regulates quantity by expression	0.2	Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.	SIGNOR-261598
P45983	Q06481	1	phosphorylation	up-regulates	0.362	Phosphorylation at the thr(668) residue of app (with respect to the numbering conversion for the app 695 isoform) and the thr(736) residue of aplp2 (with respect to the numbering conversion for the aplp2 763 isoform) in their cytoplasmic domains acts as a molecular switch for their protein-protein interaction and is implicated in neural function(s) and/or alzheimer's disease pathogenesis. Here we demonstrate that both app and aplp2 can be phosphorylated by jnk at the thr(668) and thr(736) residues, respectively, in response to cellular stress.	SIGNOR-122196
P18031	P12814	1	dephosphorylation	up-regulates	0.335	Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase.	SIGNOR-141634
P12036	P49840	0	phosphorylation	down-regulates activity	0.254	Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles.	SIGNOR-279783
P29120	P01189-PRO_0000024969	1	cleavage	up-regulates quantity	0.2	POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide	SIGNOR-268724
P04626	P35222	1	phosphorylation	down-regulates activity	0.766	Second, ErbB2 phosphorylates \u03b2-catenin at Tyr 654, leading to dissociation of the E-cadherin-\u03b2-catenin membrane complex and increased signaling to Wnt target genes such as cyclin D1 ( ).	SIGNOR-279041
Q05469	Q9UQM7	0	phosphorylation	down-regulates	0.2	Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.	SIGNOR-58251
Q06124	P01116	1	dephosphorylation	up-regulates activity	0.66	Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.	SIGNOR-255982
P61006	Q9BXM7	0	phosphorylation	down-regulates activity	0.271	For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.	SIGNOR-260268
Q07960	P60953	1	gtpase-activating protein	down-regulates activity	0.905	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-260459
Q05639	P05771	0	phosphorylation	up-regulates activity	0.2	PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.	SIGNOR-263166
Q06945	P49715	0	transcriptional regulation	down-regulates	0.382	In summary, our data demonstrate that C/EBPα negatively regulates Sox4 transcription via direct DNA-binding.	SIGNOR-255675
Q13233	Q6UUV9	1	phosphorylation	up-regulates	0.321	We report on the activation oftorc1through mekk1-mediated phosphorylation.	SIGNOR-180816
O00327	Q92753	0	transcriptional regulation	up-regulates quantity by expression	0.478	RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs	SIGNOR-266852
P06493	Q13950	1	phosphorylation	up-regulates	0.479	In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.	SIGNOR-143586
P17706	P17302	1	dephosphorylation	up-regulates	0.324	Tc-ptp dephosphorylates cx43 residues y247 and y265, dephosphorylation maintained cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-src-mediated phosphorylation of cx43.	SIGNOR-205101
P78509	Q9Y5W3	0	transcriptional regulation	up-regulates quantity by expression	0.2	KLF2 transactivates the reelin promoter in K562 cells.	SIGNOR-266048
Q15797	Q9UPW6	1	transcriptional regulation	up-regulates quantity	0.2	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268934
Q96AE4	P17542	0	transcriptional regulation	up-regulates quantity by expression	0.2	TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation.	SIGNOR-259131
Q86TM6	P05067	1	ubiquitination	down-regulates quantity by destabilization	0.339	Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients.	SIGNOR-278616
Q9UGP5	Q13315	0	phosphorylation	up-regulates activity	0.354	We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.	SIGNOR-273836
Q9NWQ8	P07948	0	phosphorylation	up-regulates activity	0.725	Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr314, which recruited Csk/Ctk to suppress Lyn kinase activity.Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn.	SIGNOR-262898
Q05655	Q13541	1	phosphorylation	down-regulates activity	0.2	As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.\|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1.	SIGNOR-279100

P17252

Q15672

1

phosphorylation

up-regulates quantity by stabilization

0.2

Because most of these sites were predicted to be phosphorylated by protein kinase C (PKC), we overexpressed PKCα in several cell lines and found that it phosphorylates Twist1 on Ser-144. we observed that PKCα-mediated Twist1 phosphorylation at Ser-144 inhibits Twist1 ubiquitination and consequently stabilizes it.

SIGNOR-277429

P57078

O14641

1

phosphorylation

up-regulates activity

0.44

Co-transfection of a RIPK4-GFP fusion increased the percentage of cells containing DVL2 puncta to more than 75% ( and ), suggesting that RIPK4 facilitates DVL2 signalosome formation.|Phosphorylation of DVL2 at Ser 298 and Ser 480 by RIPK4 favored canonical Wnt signaling.

SIGNOR-279756

Q9ULH1

Q14289

0

phosphorylation

down-regulates activity

0.458

The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. Pyk2 directly phosphorylates ASAP1 on tyrosine residues in vitro and increases ASAP1 tyrosine phosphorylation when co-expressed in HEK293T cells.Phosphorylation of tyrosine 308 and 782 affects the phosphoinositide binding profile of ASAP1, and fluorimetric Arf-GTPase assays with purified proteins revealed an inhibition of ASAP1 GTPase-activating protein activity by Pyk2-mediated tyrosine phosphorylation.

SIGNOR-263186

P17252

P38936

1

phosphorylation

up-regulates activity

0.375

Binding of calmodulin to the carboxy-terminal region of p21 induces nuclear accumulation via inhibition of protein kinase c-mediated phosphorylation of ser153| When phosphorylated at Ser153, p21 is located at the cytoplasm and disrupts stress fibers.

SIGNOR-139302

Q99466

Q00987

0

ubiquitination

down-regulates

0.37

We demonstrate that the intracellular domain of notch 4 is targeted for ubiquitylation and hence degradation by the ubiquitin ligase mdm2.

SIGNOR-172826

P09619

P22681

0

polyubiquitination

down-regulates quantity by destabilization

0.629

Overexpression of wild type Cbl in NIH3T3 cells led to an enhancement of the ligand-dependent ubiquitination and subsequent degradation of the PDGFRbeta, as observed with PDGFRalpha.

SIGNOR-272549

P45983

P22736

1

phosphorylation

down-regulates

0.5

We also identified the exact phosphorylation site of jnk to be serine 95 at the n terminus of tr3, around which a classical jnk phosphorylation motif exists. Furthermore, we demonstrated that tr3 phosphorylation by jnk coincided with its ubiquitination and degradation, resulting in the loss of its mitogenic activity.

SIGNOR-149998

P68400

O43156

1

phosphorylation

down-regulates

0.2

Here we report that tel2 and tti1 are targeted for degradation within mtorc1 by the scffbxo9 ubiquitin ligase to adjust mtor signalling to growth factor availability. This process is primed by ck2, which translocates to the cytoplasm to mediate mtorc1-specific phosphorylation of tel2/tti1

SIGNOR-200240

Q8NFU7

O94813

1

transcriptional regulation

up-regulates quantity by expression

0.2

Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.

SIGNOR-259093

Q92835

P16885

1

dephosphorylation

down-regulates activity

0.312

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268455

P31749

P49815

1

phosphorylation

down-regulates activity

0.817

We demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites for PI3K-dependent S/T kinases. Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo. We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN(-/-) tumor-derived cell lines.

SIGNOR-235515

O75582

P0C0S8

1

phosphorylation

up-regulates

0.2

We found that msk1 phosphorylated histone h2a on serine 1, and mutation of serine 1 to alanine blocked the inhibition of transcription by msk1.

SIGNOR-123383

P27361

Q9UQC2

1

phosphorylation

up-regulates

0.617

Phosphorylation of grb2-associated binder 2 on serine 623 by erk mapk regulates its association with the phosphatase shp-2 and decreases stat5 activation.We and others have demonstrated that il-2-induced tyrosine phosphorylation of gab2 and its interaction with its sh2 domain-containing partners, shp-2, p85 pi3k, and crkl (5, 26, 27). we report that pretreatment of kit 225 cells with the mek inhibitor u0126, strongly decreased the characteristic shift of gab2 in response to il-2 and increased gab2/shp-2 association, an effect that could be ascribed to erk phosphorylation of serine 623.

SIGNOR-128731

Q7L9L4

Q13043

0

phosphorylation

up-regulates

0.851

Mob1, which forms a complex with lats1/2, is also phosphorylated by mst1/2, resulting in an enhanced lats1/2mob1 interaction.

SIGNOR-175841

P16104

P51812

0

phosphorylation

up-regulates activity

0.2

Herein, we found that ribosomal S6 kinase 2 (RSK2) directly phosphorylates histone H2AX at Ser139 and also at a newly discovered site, Ser16.|Phosphorylated RSK2 and histone H2AX colocalized in the nucleus following EGF treatment, and the phosphorylation of histone H2AX by RSK2 enhanced the stability of histone H2AX and prevented cell transformation induced by EGF.

SIGNOR-279349

P45985

Q9Y2U5

0

phosphorylation

up-regulates activity

0.612

Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation

SIGNOR-107695

Q13315

P04637

1

phosphorylation

up-regulates quantity by stabilization

0.843

In response to ionizing radiation (ir), atm, the gene product mutated in ataxia telangiectasia, stabilizes and activates p53 through phosphorylation of ser15 and (indirectly) ser20. Here we show that phosphorylation of p53 on ser46, a residue important for p53 apoptotic activity, as well as on ser9, in response to ir also is dependent on the atm protein kinase. one pathway involves the phosphorylation of p53 and its negative regulator mdm2 by ataxia telangiectasia mutated (atm) and chk2 causing p53 activation and stabilization.

SIGNOR-115348

P68400

P35221

1

phosphorylation

down-regulates

0.39

We demonstrate here that egfr activation results in disruption of the complex of beta-catenin and alpha-catenin, thereby abrogating the inhibitory effect of alpha-catenin on beta-catenin transactivation via ck2alpha-dependent phosphorylation of alpha-catenin at s641.

SIGNOR-161847

P10911

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.754

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-260556

P10275

P29320

0

phosphorylation

up-regulates activity

0.273

These data suggest that Etk may be able to phosphorylate AR at Y534 and Y551/552, and the interaction between the Etk SH2 domain and phosphorylated ARY551/552 may promote their association.|This is supported by our observations that the association between Etk and AR is increased after castration and Etk induces tyrosine phosphorylation of AR, leading an increase in AR stability and transcriptional activity under androgen depleted conditions.

SIGNOR-279371

Q9H2X6

Q00987

1

phosphorylation

down-regulates activity

0.537

HIPK2 inhibits both MDM2 gene and protein by, respectively, p53-dependent and independent regulations.|This p53-independent effect is likely mediated by HIPK2 catalytic activity and we found that HIPK2 phosphorylates MDM2 in vitro.

SIGNOR-279465

O00327

P20393

0

transcriptional regulation

down-regulates quantity by repression

0.671

In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.

SIGNOR-267983

P16949

P06493

0

phosphorylation

up-regulates activity

0.641

null

SIGNOR-279803

P31749

P23769

1

phosphorylation

down-regulates

0.524

We show that insulin induces gata2 phosphorylation on serine 401 in a pi-3k/akt-dependent manner. Insulin-dependent phosphorylation of serine 401 impairs gata2 translocation to the nucleus and its dna binding activity

SIGNOR-135614

P24941

Q15910

1

phosphorylation

up-regulates activity

0.547

Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1.

SIGNOR-255656

Q16566

P29475

1

phosphorylation

down-regulates activity

0.357

It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.

SIGNOR-250713

P04637

O94953

1

transcriptional regulation

up-regulates quantity by expression

0.281

KDM4B/JMJD2B is a p53 target gene that modulates the amplitude of p53 response after DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter.

SIGNOR-263729

P31749

P52789

1

phosphorylation

up-regulates activity

0.445

K63-linked ubiquitination enhances the interaction between Akt and HK2 and eventually increases HK2 phosphorylation on Thr473 and mitochondrial localization

SIGNOR-259984

P32780

Q01094

1

phosphorylation

down-regulates quantity by destabilization

0.434

TFIIH-mediated phosphorylation of E2F-1 plays a role in triggering E2F-1 degradation during S phase. E2F-1 activation domain interacts with a kinase activity which phosphorylates two sites, Ser403 and Thr433, within the activation domain. We demonstrate that TFIIH is responsible for the E2F-1 phosphorylation observed in cell extracts and that endogenous E2F-1 interacts in vivo with p62, a component of TFIIH, during S phase.

SIGNOR-251260

O60260

P05067

1

ubiquitination

down-regulates quantity

0.2

Similarly, in transgenic AD mice models, lentiviral parkin expression ubiquitinates Abeta to reduce its intracellular levels while preventing plaque deposition, and this is associated with induction of beclin dependent autophagy .|Thus, parkin reduces Abeta levels by enhancing both UPS- and autophagy dependent clearance of Abeta.

SIGNOR-278709

Q96E17

Q9UJD0

0

relocalization

up-regulates activity

0.26

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

SIGNOR-264380

P28482

P67809

1

phosphorylation

up-regulates activity

0.47

ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.

SIGNOR-279227

P06493

Q12834

1

phosphorylation

down-regulates activity

0.935

Cdk1 phosphorylates Cdc20 to negatively regulate its ability to bind and activate the APC/C.

SIGNOR-279321

P17252

Q6UVK1

1

phosphorylation

up-regulates activity

0.2

Protein kinase C (PKC)-alpha phosphorylation of recombinant NG2 cytoplasmic domain and phorbol ester-induced PKC-dependent phosphorylation of full-length NG2 expressed in U251 cells are both blocked by mutation of Thr(2256), identifying this residue as a primary phosphorylation site. PKC-alpha-mediated NG2 phosphorylation at Thr(2256) is therefore a key step for initiating cell polarization and motility.

SIGNOR-263162

Q5QNW6

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265394

Q13131

O00418

1

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

Q15637

Q8TAS1

0

phosphorylation

up-regulates

0.406

Sf1 is phosphorylated on serines 80 and 82 in vitro and in vivo. Kis can phosphorylate sf1f on serine 80 and 82 with a high efficiency that particularly relies on the anchoring of its uhm domain to sf1. Serine phosphorylation of a conserved ser80-pro81-ser82-pro83 motif rigidifies a long unstructured linker in the sf1 helix hairpin and slightly enhances rna binding.

SIGNOR-199797

P27361

Q9NRA0

1

phosphorylation

up-regulates

0.521

Sphingosine kinase type 2 activation by erk-mediated phosphorylation. site-directed mutagenesis indicated that hsphk2 is phosphorylated on ser-351 and thr-578 by erk1

SIGNOR-153387

Q13188

P67775

0

dephosphorylation

down-regulates

0.693

Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201266

P45985

O43379

0

relocalization

up-regulates activity

0.2

In the WT brain, the WDR62 scaffold organizes a protein complex including MEKK3, MKK4/7, and JNK1 to control NPC development during corticogenesis

SIGNOR-271715

P62256

P17542

0

transcriptional regulation

up-regulates quantity by expression

0.326

Tal1 expression activated UBE2H expression, whereas Tal1 knock-down reduced UBE2H expression and ubiquitin transfer activity.|Binding of Tal1 to UBE2H was confirmed by chromatin immunoprecipitation.

SIGNOR-269000

Q9UJU2

P68400

0

phosphorylation

up-regulates

0.303

Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.

SIGNOR-23958

P11511

P01100

0

transcriptional regulation

up-regulates quantity by expression

0.346

We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.

SIGNOR-254879

Q05086

P48436

1

ubiquitination

down-regulates quantity by destabilization

0.261

We show that E6-AP ubiquitinates SOX9 in vitro and in vivo and that SOX9 levels are enhanced after addition of the proteasome inhibitor bortezomib. Similar, siRNA knockdown of E6-AP and the E2 ligase Ubc9 increased cellular SOX9 amounts, supporting the notion that SOX9 may be ubiquitinated in hypertrophic chondrocytes by E6-AP and degraded by proteasomes.

SIGNOR-272134

P17181

P29597

0

phosphorylation

up-regulates activity

0.91

We demonstrate that, in vitro, p135tyk2 phosphorylates two tyrosines on IFNaR1. A phosphopeptide corresponding to the major phosphorylation site (Tyr466) binds STAT2, but not STAT1, in an SH-2-dependent manner. Furthermore, only latent, non-phosphorylated STAT2 interacts with this phosphopeptide. When this phosphopeptide is introduced into permeabilized cells, the IFN alpha-dependent tyrosine phosphorylation of both STATs is blocked. Finally, mutant versions of IFNaR1, in which Tyr466 is changed to phenylalanine, can act in a dominant negative manner to inhibit phosphorylation of STAT2.

SIGNOR-246934

P35626

Q16581

1

phosphorylation

down-regulates activity

0.2

These findings suggest that in agonist-stimulated mast cells GRK2 and GRK3 may phosphorylate C3aR at the same or distinct sites to promote receptor desensitization.

SIGNOR-279781

Q14494

P49841

0

phosphorylation

down-regulates

0.4

Glycogen synthase kinase 3 regulates expression of nuclear factor-erythroid-2 related transcription factor-1 (nrf1) and inhibits pro-survival function of nrf1

SIGNOR-193450

P63000

Q8WWN8

0

gtpase-activating protein

down-regulates activity

0.47

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-260456

Q9C0A6

P68431

1

methylation

up-regulates activity

0.2

SETD5 Exhibits Intrinsic Methyltransferase Activity on H3K36. This assay showed that SETD5 has specific histone methyltransferase activity toward K36 but not for other residues such as K4 and K27 (Figure 8B). we revealed that SETD5 is endowed with H3K36 methyltransferase, which is necessary for RNA elongation and processing and, ultimately, correct gene transcription.

SIGNOR-264620

Q9Y6Q9

Q16877

0

phosphorylation

up-regulates activity

0.326

PFKFB4, a regulatory enzyme that synthesizes an allosteric stimulator of glycolysis2, was found to be a robust stimulator of SRC-3 that co-activates estrogen receptor (ER). PFKFB4 phosphorylates SRC-3 at serine 857 (S857) enhancing its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient SRC-3 mutant S857A (SRC-3S857A) significantly abolishes SRC-3-mediated transcriptional output

SIGNOR-267269

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

O15550

O43248

1

transcriptional regulation

up-regulates quantity by expression

0.302

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260026

O14965

P57073

1

phosphorylation

up-regulates activity

0.2

Therefore, Aurora-A not only directly phosphorylates SOX8 but also promotes SOX8 transcription indirectly by regulating c-Myc protein.

SIGNOR-280189

P10636

P53778

0

phosphorylation

down-regulates activity

0.525

Phosphorylation of tau by SAPK3 and SAPK4 markedly reduced the ability of tau to promote microtubule assembly. SAPK3 (also called ERK6 and p38) and SAPK4 phosphorylate recombinant tau protein at multiple Ser/Thr-Pro sites that are hyperphosphorylated in PHF-tau, with SAPK4 and SAPK3 being the most effective.

SIGNOR-250087

Q13976

P41220

1

phosphorylation

up-regulates activity

0.68

Thus, PKGI-alpha binds to, phosphorylates and activates RGS-2, attenuating receptor-mediated vascular contraction.

SIGNOR-249241

Q14596

P49841

0

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

P17252

Q8NFA2

1

phosphorylation

up-regulates

0.2

Phosphorylation of thr341 allows noxo1 to sufficiently interact with noxa1, an interaction that participates in nox1 activation.

SIGNOR-202482

Q14978

P17612

0

phosphorylation

up-regulates

0.307

Here we demonstrate that protein kinase a (pka)-dependent phosphorylation of nopp140 at ser 627, together with c/ebpbeta, induces agp gene expression synergistically.

SIGNOR-91186

O14757

Q08050

1

phosphorylation

up-regulates activity

0.371

In addition, upon treatment with genotoxic agents, the checkpoint kinases Chk1 and Chk2 also phosphorylate and activate FOXM1.

SIGNOR-280224

P01903

P48382

0

transcriptional regulation

up-regulates quantity by expression

0.503

In this report, we correlate the loss of IFN-γ induction of MHC class II genes with the identification of a molecular defect in an essential regulator, namely RFX5. | We have further confirmed this finding by showing that new RFX5 leucine mutants created in vitro are incapable of transactivating a class II promoter, suggesting the identification of residues essential for RFX activity.

SIGNOR-266228

Q13131

Q9P1W9

0

phosphorylation

down-regulates activity

0.2

Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth.

SIGNOR-277471

Q13085

P54646

0

phosphorylation

down-regulates

0.697

Significant negative linear correlations between phospho-acc and acc activity were observed in all models (p < 0.01). The decline in acc activity was related to the decrease in pcr and the rise in amp. A relationship between phospho-ampk (threonine 172) and activity of ampk immunoprecipitated with anti-alpha(2) subunit antibody preparation was also observed.

SIGNOR-87583

P05106

P31749

0

phosphorylation

down-regulates activity

0.613

A survey of several protein kinases revealed that Thr-753 was avidly phosphorylated by PDK1 and Akt/PKB in vitro. These observations suggest that activation of PDK1 and/or Akt/PKB in platelets may modulate the binding activity and/or specificity of beta(3) for signaling molecules.

SIGNOR-252552

Q96LC7

P06239

0

phosphorylation

up-regulates

0.26

These results suggest that the tyrosines at positions 597 and 667, contained within itim-like motifs, are likely targets of phosphorylation by several classes of signaling molecules, including lck, jak3, and emt. The tyrosine located at position y691 was also contributing to the phosphorylation of the wild-type siglec tail by lck and jak3 kinases. Y597 and y667 are likely involved in intracellular signaling

SIGNOR-112491

P42226

P23458

0

phosphorylation

up-regulates activity

0.765

IL-4-stimulated Stat6 activation is mediated by Jak1 whereas Tyk2 is required for Stat6 activation in IL-13-treated monocytes

SIGNOR-249531

O94763

P23443

0

phosphorylation

down-regulates activity

0.344

Here we report that the prefoldin chaperone URI represents a mitochondrial substrate of S6K1. In growth factor-deprived or rapamycin-treated cells, URI forms stable complexes with protein phosphatase (PP)1gamma at mitochondria, thereby inhibiting the activity of the bound enzyme. Growth factor stimulation induces disassembly of URI/PP1gamma complexes through S6K1-mediated phosphorylation of URI at serine 371.

SIGNOR-262943

P35222

P18031

0

dephosphorylation

up-regulates activity

0.66

PTP1B modulates the association of beta-catenin with N-cadherin through binding to an adjacent and partially overlapping target site.|The nonreceptor tyrosine phosphatase PTP1B associates with the cytoplasmic domain of N-cadherin and may regulate cadherin function through dephosphorylation of beta-catenin.|Thus, interaction of PTP1B with N-cadherin is essential for its association with beta-catenin, stable expression at the cell surface, and consequently, cadherin function.

SIGNOR-277121

Q86YT6

P54132

1

ubiquitination

down-regulates quantity by destabilization

0.281

BLM is Ubiquitinated by E3 Ligase MIB1.|Moreover, MIB1 mediated BLM degradation in G1 phase appears to be important for DNA double-strand break repair.

SIGNOR-278548

Q96EB6

O43524

1

deacetylation

up-regulates activity

0.911

Sirt1 increased foxo3's ability to induce cell cycle arrest and resistance to oxidative stress

SIGNOR-122405

P00519

P53350

1

phosphorylation

up-regulates activity

0.29

C-ABL can directly phosphorylate PLK1 and activate PLK1. | The above results indicate that c-ABL–mediated PLK1 Y425 phosphorylation regulates PLK1 ubiquitination and stability.

SIGNOR-260935

P00519

P40763

1

phosphorylation

up-regulates activity

0.445

Previously, we showed that c-Abl and Arg promote phosphorylation of the STAT3 transcription factor (Y705) in a variety of cancer cell lines , .|Since c-Abl and Arg activate STAT3, we investigated whether c-Abl and Arg regulate NF-kappaB signaling.

SIGNOR-279675

Q16539

Q16644

1

phosphorylation

up-regulates activity

0.714

These results, taken together, suggest the importance of the docking interaction in the efficient phosphorylation and activation of 3pk by p38.

SIGNOR-235451

Q00536

O43663

1

phosphorylation

up-regulates activity

0.344

Mechanistically, CDK16 exerts its function by phosphorylating protein regulator of cytokinesis 1 (PRC1) to regulate spindle formation during mitosis.|Indeed, immunoblot analysis showed that PRC1 phosphorylation at the T481 site (CDK-dependent major phosphorylation site) fluctuated with the abundance of CDK16 protein in the cell cycle process

SIGNOR-273017

P51812

Q96RK0

1

phosphorylation

down-regulates

0.2

Specifically, 14-3-3 binds to p90(rsk)-phosphorylated ser?_??_ Of capic?_A thereby modulating dna binding to its hmg (high-mobility group) box, whereas erk phosphorylations prevent binding of a c-terminal nls (nuclear localization sequence) to importin ?4 (kpna3)

SIGNOR-169887

O75628

Q15139

0

phosphorylation

up-regulates activity

0.356

We found that activation of protein kinase D1, a protein kinase downstream of α(1)-adrenergic signaling, leads to direct phosphorylation of Rem1 at Ser18. This results in an increase of the channel activity and plasma membrane expression observed by using a combination of electrophysiology, live cell confocal microscopy, and immunohistochemistry in heterologous expression system and neonatal cardiomyocytes.

SIGNOR-273832

Q9H2X6

P12931

0

phosphorylation

up-regulates activity

0.307

Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.

SIGNOR-278989

Q14258

P11308

1

ubiquitination

down-regulates quantity

0.301

We demonstrate that TRIM25 polyubiquitinates ERG in vitro and that inactivation of TRIM25 resulted in reduced polyubiquitination and stabilization of ERG.|Our previous discovery of USP9X as an ERG stabilizing deubiquitinase suggests that reduction of ERG protein levels by TRIM25 mediated proteasomal degradation is prevented by expression of USP9X in fusion positive prostate cancer cells.|Using several biochemical assays we show that TRIM25 mediates the polyubiquitination of full-length ERG as well as N-terminally truncated ERG.

SIGNOR-278732

P11308

P56704

1

transcriptional regulation

up-regulates quantity by expression

0.2

Interestingly, our data showed that ERG drastically induced Wnt ligand gene expression.

SIGNOR-261598

P45983

Q06481

1

phosphorylation

up-regulates

0.362

Phosphorylation at the thr(668) residue of app (with respect to the numbering conversion for the app 695 isoform) and the thr(736) residue of aplp2 (with respect to the numbering conversion for the aplp2 763 isoform) in their cytoplasmic domains acts as a molecular switch for their protein-protein interaction and is implicated in neural function(s) and/or alzheimer's disease pathogenesis. Here we demonstrate that both app and aplp2 can be phosphorylated by jnk at the thr(668) and thr(736) residues, respectively, in response to cellular stress.

SIGNOR-122196

P18031

P12814

1

dephosphorylation

up-regulates

0.335

Here we report that protein-tyrosine phosphatase 1b (ptp 1b) is an ?-Actinin phosphatase.

SIGNOR-141634

P12036

P49840

0

phosphorylation

down-regulates activity

0.254

Our results demonstrate that whereas GSK-3 alpha, GSK-3 beta, and cdk-5 will all phosphorylate NF-H, they generate different antibody reactivity profiles.

SIGNOR-279783

P29120

P01189-PRO_0000024969

1

cleavage

up-regulates quantity

0.2

POMC is post-translationally cleaved by prohormone convertase enzymes 1 and 2 (PC1, PC2) into ACTH, an N-terminal glycopeptide

SIGNOR-268724

P04626

P35222

1

phosphorylation

down-regulates activity

0.766

Second, ErbB2 phosphorylates \u03b2-catenin at Tyr 654, leading to dissociation of the E-cadherin-\u03b2-catenin membrane complex and increased signaling to Wnt target genes such as cyclin D1 ( ).

SIGNOR-279041

Q05469

Q9UQM7

0

phosphorylation

down-regulates

0.2

Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.

SIGNOR-58251

Q06124

P01116

1

dephosphorylation

up-regulates activity

0.66

Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling.

SIGNOR-255982

P61006

Q9BXM7

0

phosphorylation

down-regulates activity

0.271

For Rab8a, it was shown that serine 111 phosphorylation (pS111) is dependent on the protein kinase PINK1 and that mimicking the phosphorylation at S111 by a serine/glutamate substitution (S111E) impaired Rab8a activation by its cognate nucleotide exchange factor (GEF) Rabin8.

SIGNOR-260268

Q07960

P60953

1

gtpase-activating protein

down-regulates activity

0.905

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-260459

Q05639

P05771

0

phosphorylation

up-regulates activity

0.2

PKCβI phosphorylates eEF1A at Ser53.our proteomics exploration of cPKC signaling in the nuclei of C2C12 cells demonstrated that the up-regulation of eEF1A intranuclear content, evoked by insulin, is associated with an increase in the phosphorylation of the Ser53 residue of the protein.

SIGNOR-263166

Q06945

P49715

0

transcriptional regulation

down-regulates

0.382

In summary, our data demonstrate that C/EBPα negatively regulates Sox4 transcription via direct DNA-binding.

SIGNOR-255675

Q13233

Q6UUV9

1

phosphorylation

up-regulates

0.321

We report on the activation oftorc1through mekk1-mediated phosphorylation.

SIGNOR-180816

O00327

Q92753

0

transcriptional regulation

up-regulates quantity by expression

0.478

RORβ and RORγ are also able to induce Bmal1 activity; however, RORα4 appears the most effective in inducing this activity. The ROREs in the Bmal1 promoter also bind ROR receptors. Overexpression of RORα1 and RORα4 induces Bmal1-promoter activity by interacting with these ROREs

SIGNOR-266852

P06493

Q13950

1

phosphorylation

up-regulates

0.479

In vitro kinase assays using recombinant cdc2 kinase showed that runx2 was phosphorylated at ser(451) the cdc2 inhibitor roscovitine dose dependently inhibited in vivo runx2 dna-binding activity during mitosis and the runx2 mutant s451a exhibited lower dna-binding activity and reduced stimulation of anchorage-independent growth relative to wild type runx2.

SIGNOR-143586

P17706

P17302

1

dephosphorylation

up-regulates

0.324

Tc-ptp dephosphorylates cx43 residues y247 and y265, dephosphorylation maintained cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-src-mediated phosphorylation of cx43.

SIGNOR-205101

P78509

Q9Y5W3

0

transcriptional regulation

up-regulates quantity by expression

0.2

KLF2 transactivates the reelin promoter in K562 cells.

SIGNOR-266048

Q15797

Q9UPW6

1

transcriptional regulation

up-regulates quantity

0.2

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268934

Q96AE4

P17542

0

transcriptional regulation

up-regulates quantity by expression

0.2

TAL1 directly activates the FUBP1 promoter, leading to increased FUBP1 expression during erythroid differentiation.

SIGNOR-259131

Q86TM6

P05067

1

ubiquitination

down-regulates quantity by destabilization

0.339

Thus, HRD1 ubiquitinates and degrades denaturated APP as well as unfolded proteins, suggesting that HRD1 affects APP-A\u03b2 dynamics in the brains of AD patients.

SIGNOR-278616

Q9UGP5

Q13315

0

phosphorylation

up-regulates activity

0.354

We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.

SIGNOR-273836

Q9NWQ8

P07948

0

phosphorylation

up-regulates activity

0.725

Here we show that Lyn interacts with C-terminal Src kinase-binding protein (Cbp), an adaptor protein that recruits negative regulators C-terminal Src kinase (Csk)/Csk-like protein-tyrosine kinase (Ctk). Lyn phosphorylated Cbp on several tyrosine residues, including Tyr314, which recruited Csk/Ctk to suppress Lyn kinase activity.Thus, a single phosphotyrosine residue on Cbp coordinates a two-phase process involving distinct negative regulatory pathways to inactivate, then degrade, Lyn.

SIGNOR-262898

Q05655

Q13541

1

phosphorylation

down-regulates activity

0.2

As shown for serum, phosphorylation of 4E-BP1 by PKCdelta inhibits the interaction between 4E-BP1 and eIF4E and stimulates cap-dependent translation.|Here we demonstrate that protein kinase Cdelta (PKCdelta) associates with RAFT1 and that PKCdelta is required for the phosphorylation and inactivation of 4E-BP1.

SIGNOR-279100