GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q13233	Q4V328	binding	up-regulates activity	0.312	To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons.	SIGNOR-260640
P13224	P17612	phosphorylation	down-regulates activity	0.312	Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.	SIGNOR-249986
P48048	P12931	phosphorylation	down-regulates	0.312	Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1	SIGNOR-97803
P12830	P48729	phosphorylation	down-regulates activity	0.312	Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts\|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846	SIGNOR-274045
P30301	P17612	phosphorylation	down-regulates activity	0.312	Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed.	SIGNOR-250018
Q9HCD6	P78352	binding	up-regulates activity	0.312	In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. our results indicate that TANC-dependent spine/synapse maintenance requires TANC binding to PSD-95, which promotes synaptic localization of TANC proteins. Thus, it is likely that interaction with PSD-95 concentrates TANC proteins at synapses, where they play a role in mediating PSD-95-dependent maintenance of spines and synapses.	SIGNOR-266895
Q14457	Q13043	phosphorylation	up-regulates activity	0.312	These results suggest that Mst1 directly stimulates interaction between Beclin1 and Bcl-2.\|We here demonstrate that Mst1-induced phosphorylation of Beclin1 in its BH3 domain at Thr 108 promotes binding of Beclin1 with Bcl-2/Bcl-xL.	SIGNOR-278502
Q9NR80	P12931	phosphorylation	up-regulates	0.312	This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.	SIGNOR-179601
Q9Y2K6	P17612	phosphorylation	down-regulates quantity by destabilization	0.311	Upon β2AR activation, a specific isoform of the second messenger cAMP-dependent protein kinase A (PKAα) rapidly phosphorylates USP20 on serine 333 located in its unique insertion domain. This phosphorylation of USP20 correlates with a characteristic SDS-PAGE mobility shift of the protein, blocks its deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of the ubiquitinated β2AR to autophagosomes, which fuse with lysosomes to form autolysosomes where receptors are degraded.	SIGNOR-273795
P24928	P28482	phosphorylation	down-regulates	0.311	Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.	SIGNOR-120160
P37231	Q9GZV5	binding	down-regulates	0.311	Kmp also enhanced the association of taz with ppar_, thereby suppressing the gene transcription of ppar_ targets and resulting in diminished adipocyte differentiation.	SIGNOR-195215
P28329	Q05655	phosphorylation	up-regulates quantity	0.311	Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.	SIGNOR-249272
Q05516	O15550	transcriptional regulation	up-regulates quantity by expression	0.311	UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells.	SIGNOR-260038
Q14790	P07948	phosphorylation	down-regulates activity	0.311	The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis.	SIGNOR-272980
P45983	Q4V328	binding	up-regulates activity	0.311	To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons. GRASP-1 potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of GRASP-1 to both JNK and the upstream JNK pathway activator MEKK-1.	SIGNOR-260639
P42574	P49137	phosphorylation	up-regulates activity	0.311	MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.\|Over-expression of MK2 led to an increase in nuclear caspase-3 activity.	SIGNOR-278960
Q9Y4K3	Q04721	binding	down-regulates activity	0.311	NOTCH2 attenuated the TRAF6-AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial-mesenchymal transition (EMT) and eventually suppressed NPC metastasis.	SIGNOR-265562
P49841	Q5VWQ8	binding	up-regulates activity	0.311	DAB2IP activates GSK-3β and antagonizes Wnt-mediated EMT. GSK-3β appears to directly associate with DAB2IP. Because DAB2IP is not a phosphatase, the mechanism of GSK-3β activation by DAB2IP is likely mediated by a separate phosphatase associated within this complex. PP2A is critical for DAB2IP-mediated GSK-3β activation and MET responses.	SIGNOR-254752
P35611	P17612	phosphorylation	down-regulates activity	0.311	Protein kinase A phosphorylates -adducin at three sites in the neck domain (Ser-408, ’436, and ’481) in addition to the MARCKS-related domain of both subunits. Phosphorylation by PKA, in contrast to PKC, reduced affinity of erythrocyte adducin for spectrin-F-actin complexes as well as activity of adducin in promoting binding of spectrin to F-actin.	SIGNOR-250331
O95837	O43603	binding	up-regulates activity	0.311	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-257136
Q14676	Q9Y294	binding	up-regulates activity	0.311	Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks.	SIGNOR-277621
Q96RU2	Q13315	phosphorylation	up-regulates activity	0.311	These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.	SIGNOR-279007
P04049	O15530	phosphorylation	up-regulates activity	0.311	PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP.	SIGNOR-280063
P43405	O14757	phosphorylation	down-regulates	0.311	We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation.	SIGNOR-197528
Q8WYL5	O14654	binding	up-regulates activity	0.311	Insulin Receptor Substrate-4 Binds to Slingshot-1 Phosphatase and Promotes Cofilin Dephosphorylation. In addition, IRS4 co-localized with SSH1 in F-actin-rich membrane protrusions in insulin-stimulated cells, which suggests that the association of IRS4 with SSH1 contributes to localized activation of cofilin in membrane protrusions.	SIGNOR-277617
P20265	P49335	binding	up-regulates activity	0.311	POU proteins (Brain-1, Brain-2, Brain-4 and SCIP) serve as transcriptional transactivators. if they were to form homomeric and heteromeric complexes with each other, depending on the particular combination, they might have different DNA-binding specificities and, thus, activate different genes.	SIGNOR-220080
P29474	P54760	phosphorylation	up-regulates activity	0.311	These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.	SIGNOR-279172
P63104	P11309	phosphorylation	up-regulates activity	0.31	PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28.	SIGNOR-277574
P19419	Q9UL54	phosphorylation	up-regulates activity	0.31	Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.	SIGNOR-246638
P27361	Q9BVJ7	dephosphorylation	down-regulates activity	0.31	In particular, DUSP23 can dephosphorylate and inactivate MAPK3 ( xref ).\|In particular, DUSP23 can dephosphorylate and inactivate MAPK3.	SIGNOR-277103
Q02078	Q99623	binding	down-regulates	0.31	Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.	SIGNOR-235840
P09467	Q13263	ubiquitination	down-regulates quantity by destabilization	0.31	In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28.	SIGNOR-267591
Q96SB3	P17612	phosphorylation	down-regulates activity	0.31	Spinophilin is phosphorylated in vitro by protein kinase A (PKA). two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged.	SIGNOR-250035
Q8TDQ0	Q08881	phosphorylation	up-regulates activity	0.31	When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells.	SIGNOR-273644
P56915	O00308	ubiquitination	up-regulates activity	0.31	These results indicated that Wwp2 augments the transcription activity of Gsc.\|We confirmed that Gsc was being mono-ubiquitinated by Wwp2 via in vitro ubiquitination assays that utilized purified Gsc, recombinant Wwp2 and ubiquitin-K0 proteins that resulted in a pattern of Gsc ubiquitination similar to WT ubiquitin (XREF_FIG).	SIGNOR-278797
P04637	Q92585	binding	up-regulates	0.31	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-180136
P09471	P18089	binding	up-regulates activity	0.31	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-256993
P22001	P12931	phosphorylation	up-regulates	0.31	The shaker family k+ channel protein, kv1.3, is tyrosine phosphorylated by v-src kinase at tyr137 and tyr449 to modulate current magnitude and kinetic properties.	SIGNOR-114641
Q9Y4X5	Q13617	binding	up-regulates activity	0.31	Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.	SIGNOR-268845
P45985	Q7Z6J0	binding	up-regulates	0.31	We confirmed that posh binds activated rac1 and find that it also binds all mlk family members tested and interacts with mkk4/7 as well as jnk1 and jnk2.	SIGNOR-96952
Q9NY65	Q8NG68	tyrosination	down-regulates	0.31	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176930
Q9Y4P1	P31749	phosphorylation	up-regulates activity	0.31	In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.\| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.	SIGNOR-275834
Q14896	Q5VU43	binding	up-regulates	0.31	This study ascribes a novel function to mmgl isoform 4: it meets all criteria for classification as an akap, and we show that is involved in the phosphorylation of cmybpc as well as ctni, hence mmgl is an important regulator of cardiac contractility.	SIGNOR-173766
P78527	Q13535	phosphorylation	up-regulates	0.31	Finally, in vitro atr-mediated phosphorylation at the t2609 cluster was further confirmed by western blot analysis using phosphospecific antibodies against t2647 (fig. ?(Fig.7e),7e), suggesting that dna-pkcs could be the direct target of atr kinase.	SIGNOR-148722
P15172	Q13207	binding	down-regulates activity	0.31	We have found that TBX2 is highly up regulated in both ERMS and ARMS subtypes of RMS and demonstrate that TBX2 is a repressor of myogenesis by binding to MyoD and myogenin and inhibiting their activity.	SIGNOR-251560
P12830	P15923	transcriptional regulation	down-regulates quantity by repression	0.31	The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). \|In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation	SIGNOR-275654
P23771	Q99717	transcriptional regulation	up-regulates quantity	0.31	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-268943
P48637	Q16236	transcriptional regulation	up-regulates quantity by expression	0.31	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy	SIGNOR-279870
P46060	P68400	phosphorylation	up-regulates	0.31	Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase	SIGNOR-143948
Q9P2P6	P53350	phosphorylation	down-regulates quantity by destabilization	0.309	NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.	SIGNOR-279806
P29474	P05771	phosphorylation	down-regulates activity	0.309	The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites	SIGNOR-251630
P14921	Q13554	phosphorylation	down-regulates activity	0.309	Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites \| Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1	SIGNOR-250684
Q14694	Q13131	phosphorylation	up-regulates activity	0.309	Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10.	SIGNOR-277207
Q15942	P06493	phosphorylation	up-regulates activity	0.309	As predicted by our hypothesis, the Cdc2 dependent phosphorylation has been shown to allow the full-length zyxin to interact with h-warts and LATS1 (XREF_FIG A).\|Phosphorylation of Zyxin by Cdc2 Regulates Binding to h-warts and LATS1.	SIGNOR-279498
P16949	P17612	phosphorylation	down-regulates	0.309	Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka).	SIGNOR-38318
O95997	Q9UQM7	phosphorylation	down-regulates quantity by destabilization	0.309	CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase	SIGNOR-276381
P08670	P17612	phosphorylation	down-regulates activity	0.309	Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure.	SIGNOR-250068
P33076	P17612	phosphorylation	down-regulates activity	0.309	Downregulation of ciita function by protein kinase a (pka)-mediated phosphorylation phosphorylation at ciita serines 834 and 1050 accounts for the inhibitory effects of pka on ciita-driven class ii mhc transcription.	SIGNOR-108569
P29474	Q14289	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
O43435	Q9UBL3	binding	up-regulates activity	0.309	Tbx1 interacts with Ash2l in both yeast and mammalian cells and Ash2l acts as a transcriptional co-activator in luciferase reporter assays.	SIGNOR-251868
P02818	P25774	cleavage	down-regulates quantity by destabilization	0.309	This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.	SIGNOR-256323
Q13127	P53350	phosphorylation	down-regulates activity	0.309	Mass spectrometry revealed that PLK1 phosphorylates REST on serine-1030 ( xref and xref ).\|Notably, PLK1 depletion significantly increased REST protein half-life (XREF_FIG, XREF_SUPPLEMENTARY), indicating PLK1 antagonizes REST abundance by restraining REST protein stability.	SIGNOR-279380
O60346	P48729	phosphorylation	down-regulates quantity by destabilization	0.309	We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.	SIGNOR-276262
P35548	Q9Y458	transcriptional regulation	down-regulates quantity by repression	0.309	the main function of TBX22 as shown in misexpression experiments is to decrease proliferation. We subsequently uncovered three targets of TBX22, DLX5, MSX2, and TBX22 itself. All are downregulated in the presence of viral-derived hTBX22.	SIGNOR-265567
O14965	P12931	phosphorylation	up-regulates activity	0.309	We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement.	SIGNOR-279286
P04792	P23443	phosphorylation	down-regulates	0.309	Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.	SIGNOR-186959
Q07666	Q8N9N5	binding	down-regulates activity	0.309	SMAR1 Interacts with Sam68 in a Signal-Dependent Manner. HDAC6 in complex with SMAR1 deacetylates Sam68. Here, we document that SMAR1, in cooperation with histone deacetylase 6 (HDAC6), interacts with Sam68 and maintains it in a deacetylated state, concomitantly inhibiting the inclusion of CD44 alternate exons.	SIGNOR-266201
P14921	Q9UQM7	phosphorylation	down-regulates	0.309	Treatment of ets1 by t-cell nuclear extract or phosphorylation of these four serines by calmodulin-dependent kinase ii (camk ii) has recently been reported to decrease ets1 dna binding by reinforcing autoinhibition	SIGNOR-96334
Q92963	Q13129	binding	up-regulates activity	0.309	Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.	SIGNOR-220799
P21796	Q5TGU0	binding	up-regulates activity	0.309	Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.	SIGNOR-261826
P11362	P28482	phosphorylation	down-regulates	0.309	Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling	SIGNOR-200880
Q9UGP5	Q7Z6Z7	polyubiquitination	down-regulates quantity by destabilization	0.309	We found that Pol λ can be ubiquitinated by the E3 ligase Mule in vitro and in vivo and that this interaction is functionally connected to the phosphorylation-dependent stabilization of Pol λ by Cdk2/cyclinA.	SIGNOR-272904
P53396	P17612	phosphorylation	up-regulates activity	0.309	Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser 454, which is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PKA)	SIGNOR-250328
Q8IWA4	Q9UKV5	polyubiquitination	down-regulates quantity by destabilization	0.309	Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2.	SIGNOR-272886
Q13009	P48729	phosphorylation	down-regulates quantity by destabilization	0.309	Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site.	SIGNOR-276673
Q99250	P61328	binding	down-regulates activity	0.309	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253428
Q13257	Q96SN8	transcriptional regulation	up-regulates quantity by expression	0.309	These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter	SIGNOR-260313
P48431	Q9UGL1	transcriptional regulation	down-regulates quantity by repression	0.309	Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.	SIGNOR-273450
P11168	P17612	phosphorylation	down-regulates activity	0.309	GLUT2 is rapidly phosphorylated by protein kinase A following activation of adenylyl cyclase by forskolin. serines 489 and 501/503 and threonine 510 in the carboxyl-terminal tail of the transporter are the in vitro and in vivo sites of phosphorylation. Stimulation of GLUT2 phosphorylation in beta cells reduces the initial rate of 3-O-methyl glucose uptake by approximately 48% but does not change the Michaelis constant. a consequence of GLUT2 phosphorylation is a reduction of its catalytic activity.	SIGNOR-250050
Q99538	Q6R6M4	deubiquitination	down-regulates quantity by destabilization	0.309	We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.	SIGNOR-272854
Q9Y613	Q13464	phosphorylation	up-regulates	0.309	Rock phosphorylates the c-terminal residues ser1131, ser1137, and thr1141 of formin homology domain protein 1 (fhod1). Phosphorylation of fhod1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres.	SIGNOR-160548
P28482	O00141	phosphorylation	up-regulates activity	0.309	SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.	SIGNOR-276223
O96017	P62714	dephosphorylation	up-regulates activity	0.309	Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells\|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.	SIGNOR-248582
P24390	P17612	phosphorylation	up-regulates	0.309	We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends.	SIGNOR-118257
P26599	P17612	phosphorylation	down-regulates activity	0.309	PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.	SIGNOR-263149
Q93045	P17612	phosphorylation	down-regulates activity	0.309	Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation	SIGNOR-250056
Q9BXL7	P67775	dephosphorylation	down-regulates activity	0.309	NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane\|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.	SIGNOR-248650
Q13257	P12270	binding	up-regulates	0.309	Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20).	SIGNOR-181975
P28562	Q09472	acetylation	up-regulates	0.309	A recent report shows that mkp1 may also be regulated by acetylation. When raw macrophages are stimulated with lps, mkp1 becomes acetylated on lys57 by p300	SIGNOR-166581
Q2V2M9	P68400	phosphorylation	down-regulates	0.309	We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.	SIGNOR-170525
P48751	Q02156	phosphorylation	up-regulates activity	0.309	We conclude that following Ang II stimulation of cells, PKCepsilon phosphorylates serine 67 of the AE3 cytoplasmic domain, inducing the Ang II-induced increase in anion transport observed in the hypertrophic myocardium.	SIGNOR-249127
P00533	P43378	dephosphorylation	down-regulates activity	0.309	Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.\|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.	SIGNOR-277130
Q00613	P31751	phosphorylation	up-regulates activity	0.309	AKT2 also phosphorylated S326 of HSF1 but showed weak ability to activate HSF1.\|AKT2 promoted a significant increase in HSF1 activity , but the effect was modest while AKT3 had no significant effect on HSF1 activity ( Fig. 1A-C ) .	SIGNOR-279779
O75460	Q5SGD2	dephosphorylation	up-regulates activity	0.309	Overall, our study establishes that PP2Ce mediated IRE1 regulation in ER stress signaling is a potentially important molecular basis for its genetic contribution to metabolic syndrome.Lin et al. [36] have reported that different durations and composition of ER stress signaling pathways can dictate cell fate and the balance between survival and death.\|Recombinant wildtype PP2Ce, but not a phosphatase-dead mutant (PP2Ce-D302A), effectively dephosphorylated the phosphor-Ser724 site of IRE1\u03b1 protein (p-IRE1\u03b1) (A).	SIGNOR-277074
Q7Z418	Q04917	binding	down-regulates activity	0.309	Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3η. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3η with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3η accelerated the return of the K+ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes.	SIGNOR-263155
A6NI28	Q05397	phosphorylation	up-regulates activity	0.309	FAK and Src Mediated Phosphorylation of GRAF3 at Y376 Promotes Allosteric Activation.	SIGNOR-280097
P42575	P68400	phosphorylation	down-regulates	0.309	Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner.	SIGNOR-140836
Q96R06	Q9UJV3	ubiquitination	down-regulates quantity by destabilization	0.309	These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.	SIGNOR-278549
A8K4G0	P06241	phosphorylation	up-regulates activity	0.308	As CD300b phosphorylation was occurring only in the presence of both c-Fyn and DAP-12, we addressed whether tyrosine phosphorylation was required for association of CD300b and DAP-12. For this purpose, we generated a set of HA-tagged CD300b mutants affecting the transmembrane lysine (K158L), the cytoplasmic tyrosine (Y188F) or both residues.\|As expected, the CD300b double mutant could neither recruit DAP-12 nor become phosphorylated in the presence of c-Fyn kinase (Fig. 5⇑C). Association between CD300b and DAP-12 was maintained in absence of the c-Fyn kinase, indicating that phosphorylation of the adaptor was not essential for the formation of the complex (data not shown)	SIGNOR-264771
O14920	P35813	dephosphorylation	down-regulates	0.308	Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation	SIGNOR-181659

Q13233

Q4V328

0

binding

up-regulates activity

0.312

To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons.

SIGNOR-260640

P13224

P17612

0

phosphorylation

down-regulates activity

0.312

Platelet glycoprotein Ib beta is phosphorylated on serine 166 by cyclic AMP-dependent protein kinase. phosphorylation of this residue may contribute to the inhibitory actions of cyclic AMP by inhibiting collagen-induced polymerization of actin.

SIGNOR-249986

P48048

P12931

0

phosphorylation

down-regulates

0.312

Inhibition of c-src with herbimycin a significantly decreased the tyrosine phosphorylation level of romk1... tyrosine dephosphorylation enhances the exocytosis of romk1

SIGNOR-97803

P12830

P48729

0

phosphorylation

down-regulates activity

0.312

Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts|CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846

SIGNOR-274045

P30301

P17612

0

phosphorylation

down-regulates activity

0.312

Phosphorylation at one of these sites (serine 243) could be increased by A kinase in vitro. phosphorylation of MIP reconstituted into single bilayers increased the voltage dependence and long-term closures of the channels observed.

SIGNOR-250018

Q9HCD6

P78352

0

binding

up-regulates activity

0.312

In the present study, we provide evidence that TANC1 and its close relative TANC2 regulate dendritic spines and excitatory synapses. our results indicate that TANC-dependent spine/synapse maintenance requires TANC binding to PSD-95, which promotes synaptic localization of TANC proteins. Thus, it is likely that interaction with PSD-95 concentrates TANC proteins at synapses, where they play a role in mediating PSD-95-dependent maintenance of spines and synapses.

SIGNOR-266895

Q14457

Q13043

0

phosphorylation

up-regulates activity

0.312

These results suggest that Mst1 directly stimulates interaction between Beclin1 and Bcl-2.|We here demonstrate that Mst1-induced phosphorylation of Beclin1 in its BH3 domain at Thr 108 promotes binding of Beclin1 with Bcl-2/Bcl-xL.

SIGNOR-278502

Q9NR80

P12931

0

phosphorylation

up-regulates

0.312

This observation strongly argues for the positive role of tyr94 phosphorylation in egf-induced asef activation following the activation of rac1.

SIGNOR-179601

Q9Y2K6

P17612

0

phosphorylation

down-regulates quantity by destabilization

0.311

Upon β2AR activation, a specific isoform of the second messenger cAMP-dependent protein kinase A (PKAα) rapidly phosphorylates USP20 on serine 333 located in its unique insertion domain. This phosphorylation of USP20 correlates with a characteristic SDS-PAGE mobility shift of the protein, blocks its deubiquitinase activity, promotes its dissociation from the activated β2AR complex, and facilitates trafficking of the ubiquitinated β2AR to autophagosomes, which fuse with lysosomes to form autolysosomes where receptors are degraded.

SIGNOR-273795

P24928

P28482

0

phosphorylation

down-regulates

0.311

Erk1/2 are major ser-5 kinases after h2o2 treatment. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.

SIGNOR-120160

P37231

Q9GZV5

0

binding

down-regulates

0.311

Kmp also enhanced the association of taz with ppar_, thereby suppressing the gene transcription of ppar_ targets and resulting in diminished adipocyte differentiation.

SIGNOR-195215

P28329

Q05655

0

phosphorylation

up-regulates quantity

0.311

Finally, basal ChAT phosphorylation in neurons is mediated predominantly by PKC at Ser-476, with PKC activation increasing phosphorylation at Ser-440 and enhancing ChAT activity.

SIGNOR-249272

Q05516

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.311

UTX catalytic activity has been reported to upregulate expression of the master transcription factor PLZF and to modulate superenhancer accessibility in invariant natural killer T cells.

SIGNOR-260038

Q14790

P07948

0

phosphorylation

down-regulates activity

0.311

The non-receptor tyrosine kinase, Lyn, can phosphorylate caspase-8 on Tyr-397 and Tyr-465, rendering it resistant to activational cleavage and inhibiting apoptosis.

SIGNOR-272980

P45983

Q4V328

0

binding

up-regulates activity

0.311

To examine whether GRASP‐1 interacts with MEKK1 and JNK1 in neurons, co‐immunoprecipitation experiments were performed with detergent‐solubilized extracts from cultured cortical neurons. Both antiJNK1 and anti‐MEKK1 antibodies immunoprecipitated GRASP‐1 from neuronal lysates. These results suggest that GRASP‐1 interacts with MEKK1 and JNK1 in neurons. GRASP-1 potently activates JNK pathway signaling, with no effect on ERK signaling. Such JNK pathway activating activity requires binding of GRASP-1 to both JNK and the upstream JNK pathway activator MEKK-1.

SIGNOR-260639

P42574

P49137

0

phosphorylation

up-regulates activity

0.311

MK2 Phosphorylates Caspase-3, Facilitates Nuclear Translocation of Caspase 3, and Regulates Apoptosis.|Over-expression of MK2 led to an increase in nuclear caspase-3 activity.

SIGNOR-278960

Q9Y4K3

Q04721

0

binding

down-regulates activity

0.311

NOTCH2 attenuated the TRAF6-AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial-mesenchymal transition (EMT) and eventually suppressed NPC metastasis.

SIGNOR-265562

P49841

Q5VWQ8

0

binding

up-regulates activity

0.311

DAB2IP activates GSK-3β and antagonizes Wnt-mediated EMT. GSK-3β appears to directly associate with DAB2IP. Because DAB2IP is not a phosphatase, the mechanism of GSK-3β activation by DAB2IP is likely mediated by a separate phosphatase associated within this complex. PP2A is critical for DAB2IP-mediated GSK-3β activation and MET responses.

SIGNOR-254752

P35611

P17612

0

phosphorylation

down-regulates activity

0.311

Protein kinase A phosphorylates -adducin at three sites in the neck domain (Ser-408, ’436, and ’481) in addition to the MARCKS-related domain of both subunits. Phosphorylation by PKA, in contrast to PKC, reduced affinity of erythrocyte adducin for spectrin-F-actin complexes as well as activity of adducin in promoting binding of spectrin to F-actin.

SIGNOR-250331

O95837

O43603

0

binding

up-regulates activity

0.311

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-257136

Q14676

Q9Y294

0

binding

up-regulates activity

0.311

Chk1 activated by ataxia telangiectasia mutated (ATM) kinase on DNA breaks in G1 promotes NHEJ through direct phosphorylation of ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with the repair protein MDC1 and thus enhances MDC1's interaction with ATM and the stable localization of ATM at DNA breaks.

SIGNOR-277621

Q96RU2

Q13315

0

phosphorylation

up-regulates activity

0.311

These novel findings establish a direct connection between the ubiquitination of UCK1 by KLHL2 and phosphorylation of USP28 and UCK1 by ATM, which are involved in mediating drug resistance against 5'-AZA in AML patients.

SIGNOR-279007

P04049

O15530

0

phosphorylation

up-regulates activity

0.311

PDK1, but not PKCs, phosphorylate and activate Raf1 in MAPK pathway when platelets are stimulated with 2MeSADP.

SIGNOR-280063

P43405

O14757

0

phosphorylation

down-regulates

0.311

We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation.

SIGNOR-197528

Q8WYL5

O14654

0

binding

up-regulates activity

0.311

Insulin Receptor Substrate-4 Binds to Slingshot-1 Phosphatase and Promotes Cofilin Dephosphorylation. In addition, IRS4 co-localized with SSH1 in F-actin-rich membrane protrusions in insulin-stimulated cells, which suggests that the association of IRS4 with SSH1 contributes to localized activation of cofilin in membrane protrusions.

SIGNOR-277617

P20265

P49335

0

binding

up-regulates activity

0.311

POU proteins (Brain-1, Brain-2, Brain-4 and SCIP) serve as transcriptional transactivators. if they were to form homomeric and heteromeric complexes with each other, depending on the particular combination, they might have different DNA-binding specificities and, thus, activate different genes.

SIGNOR-220080

P29474

P54760

0

phosphorylation

up-regulates activity

0.311

These results suggest that activation of Eph-B4 with Ephrin-B2/Fc stimulates eNOS phosphorylation in vitro (XREF_FIG), eg, eNOS may be a downstream mediator of Eph-B4 signaling in endothelial cells.

SIGNOR-279172

P63104

P11309

0

phosphorylation

up-regulates activity

0.31

PIM1 phosphorylates the AR and 14-3-3 ζ and coordinates their interaction. PIM1 phosphorylation of the AR and 14-3-3 ζ enhances their interaction and shifts their occupancy on chromatin, resulting in 14-3-3 ζ co-regulation of AR, likely by recruiting other AR co-regulators such as hnRNPK and TRIM28.

SIGNOR-277574

P19419

Q9UL54

0

phosphorylation

up-regulates activity

0.31

Transfection studies demonstrated that TAO2 stimulates phosphorylation of the TCF Elk1 on the major activating site, Ser383, and that TAO2 stimulates transactivation of Elk1 and the related TCF, Sap1.

SIGNOR-246638

P27361

Q9BVJ7

0

dephosphorylation

down-regulates activity

0.31

In particular, DUSP23 can dephosphorylate and inactivate MAPK3 ( xref ).|In particular, DUSP23 can dephosphorylate and inactivate MAPK3.

SIGNOR-277103

Q02078

Q99623

0

binding

down-regulates

0.31

Phb2 interacts with both myod and mef2, and represses both myod- and mef2-dependent gene transcription. Furthermore, binding of phb2 to both myod and mef2 significantly decreases upon myogenic differentiation.

SIGNOR-235840

P09467

Q13263

0

ubiquitination

down-regulates quantity by destabilization

0.31

In this study, we demonstrated that the tripartite motif-containing protein 28 (TRIM28) binds directly to and promotes FBP1 for ubiquitination and degradation. MAGE-A3 and MAGE-C2, which are known to be overexpressed in HCC, can enhance TRIM28-dependent degradation of FBP1 by forming ubiquitin ligase complexes with TRIM28.

SIGNOR-267591

Q96SB3

P17612

0

phosphorylation

down-regulates activity

0.31

Spinophilin is phosphorylated in vitro by protein kinase A (PKA). two major sites of phosphorylation, Ser-94 and Ser-177, that are located within the actin-binding domain of spinophilin. Phosphorylation of spinophilin by PKA modulated the association between spinophilin and the actin cytoskeleton. phosphorylation of spinophilin reduced the stoichiometry of the spinophilin-actin interaction. In contrast, the ability of spinophilin to bind to PP1 remained unchanged.

SIGNOR-250035

Q8TDQ0

Q08881

0

phosphorylation

up-regulates activity

0.31

When we tested the effect of ITK on the Y265 mutant, we found a pronounced reduction of ITK-mediated tyrosine phosphorylation, suggesting that Y265 is specifically phosphorylated by ITK (Fig. 3B). Our results demonstrate that specific phosphorylation of Y265 of Tim-3 occurs in the presence of galectin-9, probably through a receptor-ligand interaction. Phosphorylation of Y265, which is situated in a highly conserved SH2 binding domain, could result in the recruitment of SH2 containing adaptor proteins and trigger downstream signalling events regulating the fate of Tim-3 expressing T-cells.

SIGNOR-273644

P56915

O00308

0

ubiquitination

up-regulates activity

0.31

These results indicated that Wwp2 augments the transcription activity of Gsc.|We confirmed that Gsc was being mono-ubiquitinated by Wwp2 via in vitro ubiquitination assays that utilized purified Gsc, recombinant Wwp2 and ubiquitin-K0 proteins that resulted in a pattern of Gsc ubiquitination similar to WT ubiquitin (XREF_FIG).

SIGNOR-278797

P04637

Q92585

0

binding

up-regulates

0.31

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-180136

P09471

P18089

0

binding

up-regulates activity

0.31

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-256993

P22001

P12931

0

phosphorylation

up-regulates

0.31

The shaker family k+ channel protein, kv1.3, is tyrosine phosphorylated by v-src kinase at tyr137 and tyr449 to modulate current magnitude and kinetic properties.

SIGNOR-114641

Q9Y4X5

Q13617

0

binding

up-regulates activity

0.31

Here, we provide evidence that Ariadne RBR E3 ubiquitin ligases such as TRIAD1 and HHARI can bind and be activated by CRL complexes. Whereas TRIAD1 specifically associates with CUL5–RBX2, HHARI is more promiscuous towards cullin types and associates with RBX1-associated cullins 1, 2, 3, and 4A. Interestingly, both TRIAD1 and HHARI show a strong preference for binding the neddylated form of the cullin. Our data suggest a novel function of NEDD8 in directing specific CRLs to Ariadne RBR ligases, which in turn exert influence on the levels of their cognate neddylated cullin.

SIGNOR-268845

P45985

Q7Z6J0

0

binding

up-regulates

0.31

We confirmed that posh binds activated rac1 and find that it also binds all mlk family members tested and interacts with mkk4/7 as well as jnk1 and jnk2.

SIGNOR-96952

Q9NY65

Q8NG68

0

tyrosination

down-regulates

0.31

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176930

Q9Y4P1

P31749

0

phosphorylation

up-regulates activity

0.31

In this study, we identified a novel phosphorylation site at Ser34 of ATG4B induced by AKT in HCC cells.| In brief, our results demonstrate for the first time that the phosphorylation of ATG4B at Ser34 participates in the metabolic reprogramming of HCC cells via repressing mitochondrial function, which possibly results from the Ser34 phosphorylation-induced mitochondrial enrichment of ATG4B and the subsequent inhibition of F1Fo-ATP synthase activity.

SIGNOR-275834

Q14896

Q5VU43

0

binding

up-regulates

0.31

This study ascribes a novel function to mmgl isoform 4: it meets all criteria for classification as an akap, and we show that is involved in the phosphorylation of cmybpc as well as ctni, hence mmgl is an important regulator of cardiac contractility.

SIGNOR-173766

P78527

Q13535

0

phosphorylation

up-regulates

0.31

Finally, in vitro atr-mediated phosphorylation at the t2609 cluster was further confirmed by western blot analysis using phosphospecific antibodies against t2647 (fig. ?(Fig.7e),7e), suggesting that dna-pkcs could be the direct target of atr kinase.

SIGNOR-148722

P15172

Q13207

0

binding

down-regulates activity

0.31

We have found that TBX2 is highly up regulated in both ERMS and ARMS subtypes of RMS and demonstrate that TBX2 is a repressor of myogenesis by binding to MyoD and myogenin and inhibiting their activity.

SIGNOR-251560

P12830

P15923

0

transcriptional regulation

down-regulates quantity by repression

0.31

The p21-activated kinase 5 (PAK5) is overexpressed in advanced cancer and the transcription factor E47 is a direct repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). |In this study, we found that PAK5-mediated E47 phosphorylation promoted EMT in advanced colon cancer. PAK5 interacted with E47 and phosphorylated E47 on Ser39 under hepatocyte growth factor (HGF) stimulation

SIGNOR-275654

P23771

Q99717

0

transcriptional regulation

up-regulates quantity

0.31

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-268943

P48637

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.31

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Importantly, GCLC, GCLM, GSS, and GSR are transcriptional targets of NFE2L2. Their upregulation is implicated in conferring resistance to ferroptosis across various contexts, including chemotherapy and radiation therapy

SIGNOR-279870

P46060

P68400

0

phosphorylation

up-regulates

0.31

Phosphorylation of rangap1 stabilizes its interaction with ran and ranbp1. Serine-358 (358s) was identified as the major phosphorylation site. Experiments using purified recombinant kinase and specific inhibitors such as drb and apigenin strongly suggest that casein kinase ii (ck2) is the responsible kinase

SIGNOR-143948

Q9P2P6

P53350

0

phosphorylation

down-regulates quantity by destabilization

0.309

NI indicates the noninduced control. (B) Plk1 phosphorylates STARD9-motor domain at serine 312.

SIGNOR-279806

P29474

P05771

0

phosphorylation

down-regulates activity

0.309

The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites

SIGNOR-251630

P14921

Q13554

0

phosphorylation

down-regulates activity

0.309

Increased Transactivation of the GM-CSF Promoter/Enhancer by Ets1 with Mutated CaMK II Sites | Significantly, phosphorylation of Ets1 by Ca2+-dependent pathways is thought to inhibit DNA binding in vitro. To analyze the role of these four serines, S251, S257, S282, and S285, in transcription, we constructed three mutant derivatives of human Ets1

SIGNOR-250684

Q14694

Q13131

0

phosphorylation

up-regulates activity

0.309

Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10.

SIGNOR-277207

Q15942

P06493

0

phosphorylation

up-regulates activity

0.309

As predicted by our hypothesis, the Cdc2 dependent phosphorylation has been shown to allow the full-length zyxin to interact with h-warts and LATS1 (XREF_FIG A).|Phosphorylation of Zyxin by Cdc2 Regulates Binding to h-warts and LATS1.

SIGNOR-279498

P16949

P17612

0

phosphorylation

down-regulates

0.309

Phosphorylation at either ser(16) or ser(63) strongly reduced or abolished the ability of stathmin to bind to and sequester soluble tubulin and its ability to act as a catastrophe factor by directly binding to the microtubules. The known in vivo phosphorylation sites of stathmin are ser-16 and ser-63 for cyclic amp-dependent protein kinase (pka).

SIGNOR-38318

O95997

Q9UQM7

0

phosphorylation

down-regulates quantity by destabilization

0.309

CaMKII phosphorylates securin at PP2A substrate site(s).Securin is destabilized by phosphorylation and stabilized by PP2A-dependent dephosphorylation on separase

SIGNOR-276381

P08670

P17612

0

phosphorylation

down-regulates activity

0.309

Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure.

SIGNOR-250068

P33076

P17612

0

phosphorylation

down-regulates activity

0.309

Downregulation of ciita function by protein kinase a (pka)-mediated phosphorylation phosphorylation at ciita serines 834 and 1050 accounts for the inhibitory effects of pka on ciita-driven class ii mhc transcription.

SIGNOR-108569

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

O43435

Q9UBL3

0

binding

up-regulates activity

0.309

Tbx1 interacts with Ash2l in both yeast and mammalian cells and Ash2l acts as a transcriptional co-activator in luciferase reporter assays.

SIGNOR-251868

P02818

P25774

0

cleavage

down-regulates quantity by destabilization

0.309

This study has been undertaken to compare the degradation of BGP by the cysteine proteinases cathepsins L, B, H, S, and the aspartic proteinase cathepsin D. Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42.

SIGNOR-256323

Q13127

P53350

0

phosphorylation

down-regulates activity

0.309

Mass spectrometry revealed that PLK1 phosphorylates REST on serine-1030 ( xref and xref ).|Notably, PLK1 depletion significantly increased REST protein half-life (XREF_FIG, XREF_SUPPLEMENTARY), indicating PLK1 antagonizes REST abundance by restraining REST protein stability.

SIGNOR-279380

O60346

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.309

We show that the beta-TrCP-mediated degradation requires phosphorylation of PHLPP1 by casein kinase I and glycogen synthase kinase 3beta (GSK-3beta), and activation of the phosphatidylinositol 3-kinase/Akt pathway suppresses the degradation of PHLPP1 by inhibiting the GSK-3beta activity.

SIGNOR-276262

P35548

Q9Y458

0

transcriptional regulation

down-regulates quantity by repression

0.309

the main function of TBX22 as shown in misexpression experiments is to decrease proliferation. We subsequently uncovered three targets of TBX22, DLX5, MSX2, and TBX22 itself. All are downregulated in the presence of viral-derived hTBX22.

SIGNOR-265567

O14965

P12931

0

phosphorylation

up-regulates activity

0.309

We report here that Src phosphorylates and activates AURA at T288, and AURA also activates focal adhesion kinase (FAK, also known as PTK2), leading to initiation of cell movement.

SIGNOR-279286

P04792

P23443

0

phosphorylation

down-regulates

0.309

Ser-15, ser-78, and ser-82 in hsp27 (ser-15 and ser-86 in hsp25) are part of the rxxs motif, a known recognition site for p70rsk.

SIGNOR-186959

Q07666

Q8N9N5

0

binding

down-regulates activity

0.309

SMAR1 Interacts with Sam68 in a Signal-Dependent Manner. HDAC6 in complex with SMAR1 deacetylates Sam68. Here, we document that SMAR1, in cooperation with histone deacetylase 6 (HDAC6), interacts with Sam68 and maintains it in a deacetylated state, concomitantly inhibiting the inclusion of CD44 alternate exons.

SIGNOR-266201

P14921

Q9UQM7

0

phosphorylation

down-regulates

0.309

Treatment of ets1 by t-cell nuclear extract or phosphorylation of these four serines by calmodulin-dependent kinase ii (camk ii) has recently been reported to decrease ets1 dna binding by reinforcing autoinhibition

SIGNOR-96334

Q92963

Q13129

0

binding

up-regulates activity

0.309

Rit and Rin were found to interact with the known Ras binding proteins RalGDS, Rlf, and AF-6/Canoe. These interactions were GTP and effector domain dependent and suggest that RalGDS, Rlf, and AF-6 are Rit and Rin effectors.

SIGNOR-220799

P21796

Q5TGU0

0

binding

up-regulates activity

0.309

Our results demonstrate the existence of a VDAC-TSPO2-ANT complex that mediates ATP release from RBCs. We previously demonstrated that the translocase protein TSPO2 together with the voltage-dependent anion channel (VDAC) and adenine nucleotide transporter (ANT) were involved in a membrane transport complex in human red blood cells (RBCs). . The present results show that TSPO ligands induce polymerization of VDAC, coupled to activation of ATP release by a supramolecular complex involving VDAC, TSPO2 and ANT.

SIGNOR-261826

P11362

P28482

0

phosphorylation

down-regulates

0.309

Erk-mediated phosphorylation of fibroblast growth factor receptor 1 on ser777 inhibits signaling

SIGNOR-200880

Q9UGP5

Q7Z6Z7

0

polyubiquitination

down-regulates quantity by destabilization

0.309

We found that Pol λ can be ubiquitinated by the E3 ligase Mule in vitro and in vivo and that this interaction is functionally connected to the phosphorylation-dependent stabilization of Pol λ by Cdk2/cyclinA.

SIGNOR-272904

P53396

P17612

0

phosphorylation

up-regulates activity

0.309

Phosphorylation of Recombinant Human ATP:Citrate Lyase by cAMP-Dependent Protein Kinase Abolishes Homotropic Allosteric Regulation of the Enzyme by Citrate and Increases the Enzyme Activity. Ser 454, which is phosphorylated by the catalytic subunit of cAMP-dependent protein kinase (PKA)

SIGNOR-250328

Q8IWA4

Q9UKV5

0

polyubiquitination

down-regulates quantity by destabilization

0.309

Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2.

SIGNOR-272886

Q13009

P48729

0

phosphorylation

down-regulates quantity by destabilization

0.309

Phosphorylation of Ser329, Ser334, and Thr340 in Tiam1 is required for its interaction with βTrCP1. The proteolysis of Tiam1 is prevented by βTrCP silencing, inhibition of CK1 and MEK, or mutation of the Tiam1 degron site.

SIGNOR-276673

Q99250

P61328

0

binding

down-regulates activity

0.309

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

SIGNOR-253428

Q13257

Q96SN8

0

transcriptional regulation

up-regulates quantity by expression

0.309

These data indicate that CDK5RAP2 is a positive regulator of both the BUBR1 promoter and the MAD2 promoter

SIGNOR-260313

P48431

Q9UGL1

0

transcriptional regulation

down-regulates quantity by repression

0.309

Phosphorylation of KDM5B at Ser1456 attenuated the occupancy of KDM5B on the promoters of pluripotency genes.

SIGNOR-273450

P11168

P17612

0

phosphorylation

down-regulates activity

0.309

GLUT2 is rapidly phosphorylated by protein kinase A following activation of adenylyl cyclase by forskolin. serines 489 and 501/503 and threonine 510 in the carboxyl-terminal tail of the transporter are the in vitro and in vivo sites of phosphorylation. Stimulation of GLUT2 phosphorylation in beta cells reduces the initial rate of 3-O-methyl glucose uptake by approximately 48% but does not change the Michaelis constant. a consequence of GLUT2 phosphorylation is a reduction of its catalytic activity.

SIGNOR-250050

Q99538

Q6R6M4

0

deubiquitination

down-regulates quantity by destabilization

0.309

We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.

SIGNOR-272854

Q9Y613

Q13464

0

phosphorylation

up-regulates

0.309

Rock phosphorylates the c-terminal residues ser1131, ser1137, and thr1141 of formin homology domain protein 1 (fhod1). Phosphorylation of fhod1 at the three residues fully disrupts the autoinhibitory interaction, which culminates in formation of stress fibres.

SIGNOR-160548

P28482

O00141

0

phosphorylation

up-regulates activity

0.309

SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), enhanced the ERK2 activity as well as the MEK/ERK complexes formation.

SIGNOR-276223

O96017

P62714

0

dephosphorylation

up-regulates activity

0.309

Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.

SIGNOR-248582

P24390

P17612

0

phosphorylation

up-regulates

0.309

We conclude that pka phosphorylation of serine 209 is required for the retrograde transport of the kdel receptor from the golgi complex to the er from which the retrieval of proteins bearing the kdel signal depends.

SIGNOR-118257

P26599

P17612

0

phosphorylation

down-regulates activity

0.309

PKA directly phosphorylates PTB on conserved Ser-16, and PKA activation in PC12 cells induces Ser-16 phosphorylation. PTB carrying a Ser-16 to alanine mutation accumulates normally in the nucleus. However, export of this mutant protein from the nucleus is greatly reduced in heterokaryon shuttling assays. Conversely, hyperphosphorylation of PTB by coexpression with the catalytic subunit of PKA results in the accumulation of PTB in the cytoplasm.

SIGNOR-263149

Q93045

P17612

0

phosphorylation

down-regulates activity

0.309

Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A. phosphorylation negatively regulates the microtubule-depolymerizing activity of SCG10 and that all four sites participate in this regulation

SIGNOR-250056

Q9BXL7

P67775

0

dephosphorylation

down-regulates activity

0.309

NF-kappaB activation is triggered by PKCtheta-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCtheta-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane|we demonstrate that PP2A removes PKCtheta-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation.

SIGNOR-248650

Q13257

P12270

0

binding

up-regulates

0.309

Tpr directly binds to mad1 and mad2. / depletion of tpr decreases the levels of mad1 at kinetochores during prometaphase, correlating with the inability of mad1 to activate mad2, which is required for inhibiting apc(cdc20).

SIGNOR-181975

P28562

Q09472

0

acetylation

up-regulates

0.309

A recent report shows that mkp1 may also be regulated by acetylation. When raw macrophages are stimulated with lps, mkp1 becomes acetylated on lys57 by p300

SIGNOR-166581

Q2V2M9

P68400

0

phosphorylation

down-regulates

0.309

We have identified a novel striated muscle-specific splice variant of the formin fhod3 that introduces a casein kinase 2 (ck2) phosphorylation site. The specific targeting of muscle fhod3 to the myofibrils in cardiomyocytes is abolished in phosphomutants or by the inhibition of ck2. Phosphorylation of muscle fhod3 also prevents its interaction with p62/sequestosome 1 and its recruitment to autophagosomes.

SIGNOR-170525

P48751

Q02156

0

phosphorylation

up-regulates activity

0.309

We conclude that following Ang II stimulation of cells, PKCepsilon phosphorylates serine 67 of the AE3 cytoplasmic domain, inducing the Ang II-induced increase in anion transport observed in the hypertrophic myocardium.

SIGNOR-249127

P00533

P43378

0

dephosphorylation

down-regulates activity

0.309

Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.

SIGNOR-277130

Q00613

P31751

0

phosphorylation

up-regulates activity

0.309

AKT2 also phosphorylated S326 of HSF1 but showed weak ability to activate HSF1.|AKT2 promoted a significant increase in HSF1 activity , but the effect was modest while AKT3 had no significant effect on HSF1 activity ( Fig. 1A-C ) .

SIGNOR-279779

O75460

Q5SGD2

0

dephosphorylation

up-regulates activity

0.309

Overall, our study establishes that PP2Ce mediated IRE1 regulation in ER stress signaling is a potentially important molecular basis for its genetic contribution to metabolic syndrome.Lin et al. [36] have reported that different durations and composition of ER stress signaling pathways can dictate cell fate and the balance between survival and death.|Recombinant wildtype PP2Ce, but not a phosphatase-dead mutant (PP2Ce-D302A), effectively dephosphorylated the phosphor-Ser724 site of IRE1\u03b1 protein (p-IRE1\u03b1) (A).

SIGNOR-277074

Q7Z418

Q04917

0

binding

down-regulates activity

0.309

Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3η. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3η with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3η accelerated the return of the K+ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes.

SIGNOR-263155

A6NI28

Q05397

0

phosphorylation

up-regulates activity

0.309

FAK and Src Mediated Phosphorylation of GRAF3 at Y376 Promotes Allosteric Activation.

SIGNOR-280097

P42575

P68400

0

phosphorylation

down-regulates

0.309

Here we show that protein kinase (pk) ck2 phosphorylates procaspase-2 directly at serine-157. When intracellular pkck2 activity is low or downregulated by specific inhibitors, procaspase-2 is dephosphorylated, dimerized, and activated in a piddosome-independent manner.

SIGNOR-140836

Q96R06

Q9UJV3

0

ubiquitination

down-regulates quantity by destabilization

0.309

These data indicated that Mid2 was ubiquitinating Astrin at K409 and targeting Astrin for degradation during cytokinesis.

SIGNOR-278549

A8K4G0

P06241

0

phosphorylation

up-regulates activity

0.308

As CD300b phosphorylation was occurring only in the presence of both c-Fyn and DAP-12, we addressed whether tyrosine phosphorylation was required for association of CD300b and DAP-12. For this purpose, we generated a set of HA-tagged CD300b mutants affecting the transmembrane lysine (K158L), the cytoplasmic tyrosine (Y188F) or both residues.|As expected, the CD300b double mutant could neither recruit DAP-12 nor become phosphorylated in the presence of c-Fyn kinase (Fig. 5⇑C). Association between CD300b and DAP-12 was maintained in absence of the c-Fyn kinase, indicating that phosphorylation of the adaptor was not essential for the formation of the complex (data not shown)

SIGNOR-264771

O14920

P35813

0

dephosphorylation

down-regulates

0.308

Using a functional genomic approach, we have identified two protein serine/threonine phosphatases, ppm1a and ppm1b, as ikkbeta phosphatases. Overexpression of ppm1a or ppm1b results in dephosphorylation of ikkbeta at ser177 and ser181 and termination of ikkbeta-induced nf-kappab activation

SIGNOR-181659