GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q96S38	Q9NYA1	1	binding	up-regulates activity	0.384	The PSK2 domain of RPK118 is required for binding to SPHK1 as demonstrated by the results from immunoprecipitation analyses (Fig. 6) as well as yeast two-hybrid screening (Fig. 1A). The overexpression of RPK118 in COS7 cells did not cause any change in the intracellular content of SPP with repeated experiments, and RPK118 binding to SPHK1 did not alter the enzymatic activity of SPHK1 in vitro (data not shown), suggesting that RPK118 may function only as an adaptor molecule for SPHK1	SIGNOR-273744
P17252	P28329	1	phosphorylation	up-regulates	0.383	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-129264
O15111	Q86VP1	1	phosphorylation	up-regulates activity	0.383	Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).	SIGNOR-175062
Q86Y07	P04637	1	phosphorylation	up-regulates activity	0.383	Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells.\|Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation.	SIGNOR-280162
P36873	P31749	1	dephosphorylation	down-regulates activity	0.383	Here, we identify PP1 as a serine/threonine phosphatase that associates with and dephosphorylates AKT in breast cancer cells\|The heat shock protein 90 inhibitor geldanamycin and the ErbB inhibitor ZD1839 promote rapid PP1 phosphatase-dependent inactivation of AKT in ErbB2 overexpressing breast cancer cells	SIGNOR-252605
P49336	Q15797	1	phosphorylation	down-regulates	0.383	Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.	SIGNOR-161626
Q15208	P46937	1	phosphorylation	down-regulates activity	0.383	We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.	SIGNOR-259855
Q00535	P14416	1	phosphorylation	down-regulates activity	0.383	These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.	SIGNOR-259401
P28482	P49841	1	phosphorylation	down-regulates activity	0.383	We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels	SIGNOR-262524
P49841	P12931	1	phosphorylation	up-regulates activity	0.383	P -Ser9 GSK-3\u03b2 phosphorylates Ser43, Ser51, and Ser493 residues of src, regulating src activity.	SIGNOR-278444
Q9H4B4	P30304	1	phosphorylation	down-regulates	0.383	Here, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cdc25a to promote its proteolysis in early cell-cycle phases. Phosphorylation by gsk-3beta requires priming of cdc25a, and this can be catalyzed by polo-like kinase 3 (plk-3)	SIGNOR-160228
P52333	O95644	1	phosphorylation	up-regulates activity	0.383	Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.	SIGNOR-276435
Q16236	P36969	1	transcriptional regulation	up-regulates quantity by expression	0.383	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.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.	SIGNOR-279874
P24468	P15172	1	binding	down-regulates	0.383	The orphan nuclear receptor, coup-tf ii, inactivates myogenesis by post-transcriptional regulation of myod function: coup-tf ii directly interacts with p300 and myod.	SIGNOR-62248
Q8IW41	P05412	1	phosphorylation	up-regulates activity	0.383	Consequently, our study clearly determined that p38 MAP kinase-activated MK5 could trigger the activity of c-Jun through phosphorylation of c-Jun, which then bound to the SNAI1 promoter to promote SNAI1-mediated EMT.It has been reported that altering extracellular responses and intracellular signal transduction, such as enhancing the activity of p38MAPK [48], JNK [49] and eIF4 [39] signaling pathways, leads to carcinogenesis and aggravates metastasis.\|Western blot analysis showed that MK5 could promote the phosphorylation of c-Jun S63 site and the expression of SNAI1 (Fig.\u00a05a).	SIGNOR-279422
Q00535	Q96PV0	1	phosphorylation	up-regulates activity	0.383	CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.\|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.	SIGNOR-279157
Q15418	P21333	1	phosphorylation	up-regulates	0.383	We show that the n-terminal kinase domain of rsk phosphorylates flna on ser(2152) in response to mitogens	SIGNOR-123458
Q4G148	P46531	1	glycosylation	up-regulates	0.383	Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment.	SIGNOR-177691
Q96EB6	Q02577	1	deacetylation	up-regulates activity	0.383	SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter	SIGNOR-254830
P48436	O75030	1	binding	up-regulates activity	0.383	BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.	SIGNOR-255183
Q06413	P12882	1	transcriptional regulation	up-regulates quantity by expression	0.383	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238754
P68400	P11387	1	phosphorylation	up-regulates activity	0.383	In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.	SIGNOR-276155
O75116	Q16555	1	phosphorylation	up-regulates	0.383	Rho-kinase phosphorylated crmp-2 at thr-555 in vitro.we demonstrated that crmp-2 is phosphorylated by rho-kinase in drg neurons during lpa-induced growth cone collapse.	SIGNOR-77543
Q96P31	Q06124	1	binding	up-regulates activity	0.383	Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.	SIGNOR-274014
P14174	P25025	1	binding	up-regulates activity	0.382	We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.	SIGNOR-252061
P11309	P46527	1	phosphorylation	down-regulates activity	0.382	We show, herein, that all the pim family members (pim1, pim2, and pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(kip1) at threonine-157 and threonine-198 residues in cells and in vitro.\|Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels.	SIGNOR-179300
P06241	P24666	1	phosphorylation	up-regulates activity	0.382	We identify Tyr-131 as the major phosphorylation site and Tyr-132 as a minor site and the Src family PTKs Lck and Fyn as enzymes capable of phosphorylating these sites in vivo and in vitro. Both Tyr-131 and Tyr-132 are located next to the catalytic pocket of LMPTP, and especially, Tyr-131 seems to be important for the activity of LMPTP. Phosphorylation of Tyr-131 or Tyr-132, particularly the former, caused an increase in the activity of LMPTP.	SIGNOR-251150
P06239	P03372	1	phosphorylation	up-regulates	0.382	On the basis of these data and other reports describing the structure and activity of y537 mutations, as well as knowledge of the three-dimensional structure of the her ligand binding domain, we propose an alternate model wherein y537f mutation favors an open pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active closed pocket conformation.	SIGNOR-55853
P05771	Q06187	1	phosphorylation	down-regulates activity	0.382	We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. \| This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.	SIGNOR-249110
P49841	O00327	1	phosphorylation	down-regulates	0.382	Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened.	SIGNOR-162786
Q06187	P40763	1	phosphorylation	down-regulates activity	0.382	Phosphorylation of STAT-3 by BTK may also alter the conformation of STAT-3 in such a way as to make it inaccessible as a substrate of activating kinases such as JAK3.\|The ability of BTK to negatively regulate STAT-3 activity suggests several possible models for a mechanism of BTK action.	SIGNOR-279011
P49715	Q06945	1	transcriptional regulation	down-regulates	0.382	In summary, our data demonstrate that C/EBPα negatively regulates Sox4 transcription via direct DNA-binding.	SIGNOR-255675
P60484	P10636	1	dephosphorylation	up-regulates activity	0.382	Reduced phosphorylation of PTEN can dramatically increase tau phosphorylation and impair the ability of tau to bind to microtubules .	SIGNOR-277079
P24941	Q05209	1	phosphorylation	down-regulates activity	0.382	In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.	SIGNOR-277366
Q9Y5B0	P30291	1	dephosphorylation	up-regulates activity	0.382	At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.\|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to progressive loss of Cdk1 activity that weakens the SAC to a point in which the mitotic state could not be sustained .	SIGNOR-277142
Q9UBE8	P46531	1	phosphorylation	down-regulates	0.382	Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.	SIGNOR-163697
P23467	P28482	1	dephosphorylation	down-regulates	0.382	Expression of rptp-beta inhibits both mek1/2 and erk1/2 phosphorylation.	SIGNOR-173000
Q5VWQ8	O75460	1	binding	up-regulates activity	0.382	DAB2IP binds IRE1α, and was shown to be required for activation of this signaling cascade in endothelial cells. IRE1α can trigger pro-apoptotic JNK signaling through recruitment of the TRAF2–ASK1 complex. DAB2IP facilitates IRE1α activation, and participates in a signaling complex required to induce TRAF2-dependent ASK1 activation and JNK phosphorylation.	SIGNOR-254749
Q9BXH1	Q16611	1	binding	up-regulates	0.382	Bim, and puma bind with high affinity to all pro-survival proteins	SIGNOR-196929
Q9BXM7	P99999	1	null	down-regulates quantity	0.382	There is a strong cyto-protective role of PINK1 in maintaining mitochondrial homeostasis via different mechanisms. Overexpression of wild-type PINK1 in SH-SY5Y neuroblastoma cells stabilizes respiring mitochondrial networks through various mechanisms that include maintaining mitochondrial membrane potential, reducing basal and neurotoxin-induced ROS, suppression of cytochrome c release, reversal of toxin-induced fission, and suppression of autophagy	SIGNOR-249704
A0PJZ3	P46531	1	binding	up-regulates	0.382	Recently, we have shown (28) that two members of the human glycosyltransferase 8 family (gt8) (29), gxylt1 and gxylt2 (glucoside-xylosyltransferase 1/2), are able to transfer the first alfa1,3-linked xylose to o-glucosylated mammalian notch egf repeats.	SIGNOR-177714
Q15139	Q15276	1	phosphorylation	up-regulates activity	0.382	PKD phosphorylates Rabaptin-5 at Ser407, and this controls alphavbeta3 and alpha5beta1 integrin and EGFR recycling.	SIGNOR-278192
O00358	P07202	1	transcriptional regulation	up-regulates quantity by expression	0.382	TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8	SIGNOR-267279
O15105	Q8N5C8	1	binding	up-regulates	0.382	The formation of smad7-tab2 and smad7-tab3 complexes resulted in the suppression of tnf signaling.	SIGNOR-153920
Q9NXV6	P04637	1	binding	up-regulates	0.382	In the nucleoplasm, carf interacts with p53 and enhances its function.	SIGNOR-147360
P28482	P27708	1	phosphorylation	up-regulates	0.382	Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol	SIGNOR-137171
P27448	Q92974	1	phosphorylation	up-regulates activity	0.382	Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser151 This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules.	SIGNOR-277368
P00533	P0DP25	1	phosphorylation	down-regulates	0.382	Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.	SIGNOR-266335
O95747	Q13153	1	phosphorylation	down-regulates activity	0.382	OSR1 phosphorylated threonine 84 in the N-terminal regulatory domain of PAK1. phosphorylation of PAK1 by OSR1 desensitizes PAK1 to activation by small G proteins, providing a modulatory input to PAK1 activity.	SIGNOR-250210
P17252	P06730	1	phosphorylation	up-regulates	0.382	Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E .	SIGNOR-248945
P49354	P01116	1	null	up-regulates activity	0.382	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242559
Q13976	P31645	1	phosphorylation	up-regulates	0.382	These results are consistent with the hypothesis that pkg phosphorylates hsert at thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by tm5.	SIGNOR-158186
P45983	O75581	1	phosphorylation	up-regulates	0.382	We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription.	SIGNOR-169007
O75093	P35052	1	binding	up-regulates	0.382	Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.	SIGNOR-68327
P53350	P33981	1	phosphorylation	up-regulates activity	0.381	Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. Plk1 Targets Mps1 Autophosphorylation Sites In Vitro	SIGNOR-276199
Q9UMX1	Q8NEA6	1	binding	down-regulates	0.381	These data indicate that the inhibition of glis3-mediated transactivation by sufu appears to rely on the interaction with glis3 through the ygh motif and is not related to an effect on the general transcriptional machinery	SIGNOR-173573
P24941	P38432	1	phosphorylation	up-regulates	0.381	In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed	SIGNOR-84949
P63092	O15169	1	binding	up-regulates	0.381	We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.	SIGNOR-141789
P56545	P12830	1	transcriptional regulation	down-regulates quantity by repression	0.381	Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner	SIGNOR-261578
P11309	P10275	1	phosphorylation	up-regulates activity	0.381	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-277575
Q8NI17	O60674	1	binding	up-regulates	0.381	Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.	SIGNOR-161430
Q7Z6M2	P67809	1	binding	down-regulates quantity by destabilization	0.381	Here we identify FBX33 as a component of an SCF E3-ubiquitin ligase that targets the multifunctional regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and destruction by the proteasome. By targeting YB-1 for proteasomal degradation, FBX33 negatively interferes with YB-1 mediated functions. FBX33 recruits Skp-1/Cul1 to YB-1	SIGNOR-271604
P07948	Q92918	1	phosphorylation	up-regulates activity	0.381	BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.	SIGNOR-251403
P35452	Q9ULX9	1	binding	down-regulates activity	0.381	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221884
Q9NV58	P41180	1	ubiquitination	down-regulates quantity by destabilization	0.381	Coexpression with dorfin decreased the amount of total CaR protein and increased CaR ubiquitination, whereas a dominant negative fragment of dorfin had opposite effects. dorfin-mediated proteasomal degradation of immature CaR occurs from the endoplasmic reticulum. Because endogenous CaR in Madin-Darby canine kidney cells is also subject to degradation from the endoplasmic reticulum, dorfin-mediated ubiquitination may contribute to a general mechanism for CaR quality control during biosynthesis.	SIGNOR-271456
Q92793	P28069	1	binding	up-regulates activity	0.381	We and others have recently shown that CBP can constitutively bind to Pit-1 and synergistically activate transcription of promoters containing Pit-1 DNA-binding sites.	SIGNOR-267204
Q9Y6E0	Q15208	1	phosphorylation	up-regulates	0.381	Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.	SIGNOR-142467
Q9H0M0	Q9BT67	1	ubiquitination	down-regulates quantity	0.381	Accordingly, the ubiquitination assays were performed and the results revealed that knockdown of WWP1 reduced the ubiquitination of NDFIP1 in HuCCT1 and vice versa in HCCC-9810 and RBE (Fig. 7E).\|In addition, we found that WWP1 could reduce the protein level of NDFIP1 via ubiquitination.	SIGNOR-278796
Q9Y243	Q96ST2	1	phosphorylation	up-regulates activity	0.381	The data presented in this report confirmed the differential phosphorylation of IWS1 at Ser720/Thr721 by Akt3 and Akt1 and showed that its phosphorylation at this site is required for the recruitment of SetD2 to the Spt6-IWS1-Aly/REF complex.	SIGNOR-273496
P49841	Q9UBN7	1	phosphorylation	up-regulates activity	0.381	GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.\|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.\|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.	SIGNOR-278941
Q16620	P06241	1	binding	up-regulates	0.381	All these data suggest the involvement of fyn in the neurotrophin signal transduction pathways downstream of trkb. We investigated whether fyn is involved in the trk-dependent signal transduction pathways of neurotrophin. The fyn-src homology domain 2 (sh2) was observed to associate in vitro with the intracellular domain of trkb (icd-trkb).	SIGNOR-58424
P28482	P09917	1	phosphorylation	up-regulates activity	0.381	Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.	SIGNOR-264409
Q9NQS1	Q13315	2	binding	up-regulates activity	0.381	These data suggest that Aven overexpression can activate ATM and that Aven phosphorylation in a positive feedback loop enforces Aven activity, making it a more potent ATM activator.	SIGNOR-262638
Q86Y01	Q09472	1	binding	up-regulates	0.381	We found that a significant fraction of dtx1 proteins were localized in the nucleus and physically interacted with the transcriptional coactivator p300.	SIGNOR-110629
Q9BYH8	Q16552	1	transcriptional regulation	up-regulates quantity by expression	0.381	In cooperation with RORγt and RORα, IκBζ enhances Il17a expression by binding directly to the regulatory region of the Il17a gene.	SIGNOR-266210
Q13315	Q9NQS1	2	phosphorylation	up-regulates activity	0.381	Aven is also a substrate of the ATM kinase. Mutation of ATM-mediated phosphorylation sites on Aven reduced its ability to activate ATM, suggesting that Aven activation of ATM after DNA damage is enhanced by ATM-mediated Aven phosphorylation. We found that mutating S135 and S308 sites to Alanine largely dampened Aven’s phosphorylation by ATM (though some phosphorylation remained, due to either a contaminating kinase or an unidentified ATM phosphorylation site).	SIGNOR-262636
P36897	P27986	1	binding	up-regulates	0.381	These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.	SIGNOR-227525
P05129	P30086	1	phosphorylation	up-regulates activity	0.381	Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I	SIGNOR-249190
P0C2W1	Q96IZ0	1	binding	down-regulates quantity by destabilization	0.381	Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis.Fbxo45 forms an atypical ubiquitin ligase complex that contains Skp1 and the Ring-finger protein PAM (protein-associated with myc) also known as MYCBP2 (myc-binding protein 2).	SIGNOR-272223
O14965	Q9NRM7	1	phosphorylation	up-regulates	0.38	On the basis of these observations, we conclude that s83 of lats2 is a phosphorylation target of aurora-a and this phosphorylation plays a role of the centrosomal localization of lats2.	SIGNOR-124830
O15111	O75925	1	phosphorylation	up-regulates activity	0.38	In addition, we show that IKKalpha is associated with PIAS1 and mediates the S90 phosphorylation of PIAS1.\|Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to repress transcription.	SIGNOR-278926
Q96A56	P60520	1	binding	up-regulates	0.38	In this work, we show that tp53inp1 is also able to interact with atg8-family proteins and to induce autophagy-dependent cell death. mammalian cells contain multiple atg8 orthologs belonging to three subfamilies: microtubule-associated protein 1 light chain 3, -aminobutyric acid receptor-associated protein (gabarap) and -aminobutyric acid receptor-associated protein like 2 (gabarapl2).	SIGNOR-196667
Q9NWZ3	P14598	1	phosphorylation	up-regulates	0.38	Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.	SIGNOR-152027
Q6IQ23	Q5EBL8	1	binding	up-regulates activity	0.38	Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. The PLEKHA7-PDZD11 Complex Clusters ADAM10 at Junctions through Tspan33	SIGNOR-261253
P04150	Q03135	1	binding	up-regulates	0.38	He mGR appears to reside in caveolae and its association with caveolin-1 (Cav-1) was clearly detected in two of the four cell lines investigated using double recognition proximity ligation assay.	SIGNOR-251683
P01222	Q92911	1	transcriptional regulation	up-regulates quantity by expression	0.38	Iâ€“ uptake is stimulated by TSH, the master hormone for thyroid gland regulation. TSH stimulation results, at least in part, from the cAMP-mediated increase in NIS biosynthesis. TSH not only stimulates NIS transcription and biosynthesis but is also required for modulating the NIS phosphorylation pattern, maintaining its half-life, and retaining NIS at the thyrocyte plasma membrane	SIGNOR-251995
P27361	P53805	1	phosphorylation	up-regulates activity	0.38	Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively \|Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.	SIGNOR-249478
Q96GD4	Q01860	1	phosphorylation	down-regulates activity	0.38	Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.	SIGNOR-279592
P18031	Q16620	1	dephosphorylation	down-regulates activity	0.38	Collectively, these data establish a direct enzyme-substrate interaction between PTP1B and phosphorylated Y705/706 (p-Y705/706) TRKB, the critical autophosphorylation sites that mediate BDNF-induced signaling.\| Therefore, the data are consistent with a role of PTP1B as an inhibitor of BDNF/TRKB signaling	SIGNOR-264554
P17252	Q9HBA0	1	phosphorylation	up-regulates activity	0.38	We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.	SIGNOR-260882
P00519	P18206	1	phosphorylation	up-regulates activity	0.38	Abl is the tyrosine kinase that phosphorylates vinculin Y822.\|Finally we show that Abl inhibition prevents vinculin actions in cadherin containing complexes, resulting in defects in cell stiffening.	SIGNOR-278464
P14091	P01023	1	cleavage	down-regulates quantity by destabilization	0.38	Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E\|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.	SIGNOR-266977
Q8IVH8	Q04759	1	phosphorylation	up-regulates	0.38	We report that the kinase glk (map4k3) directly activated pkc-? During tcr signaling.	SIGNOR-176744
P12931	Q16832	1	phosphorylation	up-regulates	0.38	Here, using baculoviral co-expression of the ddr2 cytosolic domain and src, we show that src targets three tyrosine residues (tyr-736, tyr-740, and tyr-741) in the activation loop of ddr2 for phosphorylation. This phosphorylation by src stimulates ddr2 cis-autophosphorylation of additional tyrosine residues.	SIGNOR-140767
P18031	Q13480	1	dephosphorylation	down-regulates activity	0.38	Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well.\|The results indicate that PTP1B completely dephosphorylated Gab1 and the mutant protein failed to dephosphorylate Gab1 (Figure\u00a0 xref C).	SIGNOR-276965
Q05513	Q96RI1	1	phosphorylation	up-regulates	0.38	The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein,	SIGNOR-179771
P06241	Q13322	1	phosphorylation	down-regulates	0.38	Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.	SIGNOR-78702
Q6ZNJ1	Q96N67	1	binding	up-regulates activity	0.38	In summary, from 129 binding partners of Nbeal2 identified by mass spectrometry, we have confirmed the interaction of 3, Dock7, Sec16a, and Vac14, by different biochemical and cellular approaches\|Given the significant reduction of Dock7 levels and its altered localization in Nbeal2−/− platelets, we postulated that this canonical signaling pathway may be disrupted and set out to test this using control and Nbeal2−/− platelets.	SIGNOR-261891
P28482	Q01860	1	phosphorylation	down-regulates	0.38	We demonstrate that oct4a interacts with erk1/2 by using both in vitro gst pulldown and in vivo co-immunoprecipitation assays. Ms analysis identified phosphorylation of oct4a at ser-111. / serine 111 phosphorylation regulates oct4a protein subcellular distribution and degradation.	SIGNOR-192097
Q9H4B4	Q16143	1	phosphorylation	down-regulates activity	0.38	Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.	SIGNOR-189057

Q96S38

Q9NYA1

1

binding

up-regulates activity

0.384

The PSK2 domain of RPK118 is required for binding to SPHK1 as demonstrated by the results from immunoprecipitation analyses (Fig. 6) as well as yeast two-hybrid screening (Fig. 1A). The overexpression of RPK118 in COS7 cells did not cause any change in the intracellular content of SPP with repeated experiments, and RPK118 binding to SPHK1 did not alter the enzymatic activity of SPHK1 in vitro (data not shown), suggesting that RPK118 may function only as an adaptor molecule for SPHK1

SIGNOR-273744

P17252

P28329

1

phosphorylation

up-regulates

0.383

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.

SIGNOR-129264

O15111

Q86VP1

1

phosphorylation

up-regulates activity

0.383

Here we demonstrate that tax1bp1 was inducibly phosphorylated on ser593 and ser624 in response to proinflammatory stimuli. The kinase ikkalpha, but not ikkbeta, was required for phosphorylation of tax1bp1 and directly phosphorylated tax1bp1 in response to stimulation with tumor necrosis factor (tnf) or interleukin 1 (il-1).

SIGNOR-175062

Q86Y07

P04637

1

phosphorylation

up-regulates activity

0.383

Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells.|Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation.

SIGNOR-280162

P36873

P31749

1

dephosphorylation

down-regulates activity

0.383

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

SIGNOR-252605

P49336

Q15797

1

phosphorylation

down-regulates

0.383

Phosphorylation of the linker region of smad1, a receptor-activated smad (r-smad), at serine 206 (s206) and s214 induced by bmp and mediated by cdk8/9 is critical for binding of the e3 ubiquitin ligase smurf1. Binding of smurf1 leads to polyubiquitination of smad1 and its degradation by the proteasome;cdk8 and cyclint-cdk9 showed a preference for s206 and s214 but also phosphorylated s186 and s195 in the case of smad1;and t179, s208 and s213 in the case of smad3.

SIGNOR-161626

Q15208

P46937

1

phosphorylation

down-regulates activity

0.383

We show that mammalian NDR1/2 kinases phosphorylate YAP1 on S127 and thereby negatively regulate YAP1 activity in tissue-cultured cells.

SIGNOR-259855

Q00535

P14416

1

phosphorylation

down-regulates activity

0.383

These results indicate that Cdk5-mediated phosphorylation of S321 inhibits DRD2 function, providing a novel regulatory mechanism for dopamine signaling.

SIGNOR-259401

P28482

P49841

1

phosphorylation

down-regulates activity

0.383

We demonstrate that insulin-mediated activation of ERK1/2 results in phosphorylation of GSK3β at S9 independently of Akt/mTORC1 activity in Tsc2 null mouse embryonic fibroblasts. In addition, we show that inhibition of ERK1/2 rescues GSK3β activity and restores protein synthesis in Tsc2 −/− MEFs to normal levels

SIGNOR-262524

P49841

P12931

1

phosphorylation

up-regulates activity

0.383

P -Ser9 GSK-3\u03b2 phosphorylates Ser43, Ser51, and Ser493 residues of src, regulating src activity.

SIGNOR-278444

Q9H4B4

P30304

1

phosphorylation

down-regulates

0.383

Here, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cdc25a to promote its proteolysis in early cell-cycle phases. Phosphorylation by gsk-3beta requires priming of cdc25a, and this can be catalyzed by polo-like kinase 3 (plk-3)

SIGNOR-160228

P52333

O95644

1

phosphorylation

up-regulates activity

0.383

Here we found that IL-7-Jak3 signals activated the transcription factor NFATc1 in DN thymocytes by phosphorylating Tyr371 in the regulatory region of NFATc1.

SIGNOR-276435

Q16236

P36969

1

transcriptional regulation

up-regulates quantity by expression

0.383

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.GPX4 stands out within the GPX family due to its unique ability to reduce lipid hydroperoxides directly within cell membranes, thereby safeguarding cells from lipid peroxidation and ferroptosis.

SIGNOR-279874

P24468

P15172

1

binding

down-regulates

0.383

The orphan nuclear receptor, coup-tf ii, inactivates myogenesis by post-transcriptional regulation of myod function: coup-tf ii directly interacts with p300 and myod.

SIGNOR-62248

Q8IW41

P05412

1

phosphorylation

up-regulates activity

0.383

Consequently, our study clearly determined that p38 MAP kinase-activated MK5 could trigger the activity of c-Jun through phosphorylation of c-Jun, which then bound to the SNAI1 promoter to promote SNAI1-mediated EMT.It has been reported that altering extracellular responses and intracellular signal transduction, such as enhancing the activity of p38MAPK [48], JNK [49] and eIF4 [39] signaling pathways, leads to carcinogenesis and aggravates metastasis.|Western blot analysis showed that MK5 could promote the phosphorylation of c-Jun S63 site and the expression of SNAI1 (Fig.\u00a05a).

SIGNOR-279422

Q00535

Q96PV0

1

phosphorylation

up-regulates activity

0.383

CDK5 increases recombinant SYNGAP1 activity on Ras-GAP by 98% and its Rap-GAP activity by 20%.|Interestingly, phosphorylation of SYNGAP1 by CDK5 and CaMKII increases overall SYNGAP1 activity, but also alters the ratio of its GAP activity towards Ras- and Rap-GTPases.

SIGNOR-279157

Q15418

P21333

1

phosphorylation

up-regulates

0.383

We show that the n-terminal kinase domain of rsk phosphorylates flna on ser(2152) in response to mitogens

SIGNOR-123458

Q4G148

P46531

1

glycosylation

up-regulates

0.383

Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment.

SIGNOR-177691

Q96EB6

Q02577

1

deacetylation

up-regulates activity

0.383

SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter

SIGNOR-254830

P48436

O75030

1

binding

up-regulates activity

0.383

BEST1 promoter activity was increased by SOX9 overexpression and decreased by siRNA-mediated SOX9 knockdown. SOX9 physically interacted with MITF and OTX2 and orchestrated synergistic activation of the BEST1 promoter with the paired SOX site playing essential roles.

SIGNOR-255183

Q06413

P12882

1

transcriptional regulation

up-regulates quantity by expression

0.383

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238754

P68400

P11387

1

phosphorylation

up-regulates activity

0.383

In vitro kinase assays demonstrated that Ser(10) can be phosphorylated by casein kinase II, Ser(21) can be phosphorylated by protein kinase Calpha, and Ser(112) and Ser(394) can be phosphorylated by Cdk1.Collectively these results indicate that topo I is phosphorylated during mitosis at multiple sites, one of which enhances DNA relaxation activity in vitro and interaction with DNA in cells.

SIGNOR-276155

O75116

Q16555

1

phosphorylation

up-regulates

0.383

Rho-kinase phosphorylated crmp-2 at thr-555 in vitro.we demonstrated that crmp-2 is phosphorylated by rho-kinase in drg neurons during lpa-induced growth cone collapse.

SIGNOR-77543

Q96P31

Q06124

1

binding

up-regulates activity

0.383

Tyrosine phosphorylation of SPAP2a by c-Src and in vitro. Tyrosine-phosphorylated SPAP2 is specifically associated with SH2 domain-containing tyrosine kinases Syk and Zap70 and SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2. Site-specific mutagenesis studies revealed that tyrosyl residues 650 and 662 embedded in the ITIMs are responsible for the binding of Syk and Zap70 while tyrosyl residues 692 and 722 embedded in the ITIMs are involved in interactions with SHP-1 and SHP-2.

SIGNOR-274014

P14174

P25025

1

binding

up-regulates activity

0.382

We identify the chemokine receptors CXCR2 and CXCR4 as functional receptors for MIF [] By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis.

SIGNOR-252061

P11309

P46527

1

phosphorylation

down-regulates activity

0.382

We show, herein, that all the pim family members (pim1, pim2, and pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(kip1) at threonine-157 and threonine-198 residues in cells and in vitro.|Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels.

SIGNOR-179300

P06241

P24666

1

phosphorylation

up-regulates activity

0.382

We identify Tyr-131 as the major phosphorylation site and Tyr-132 as a minor site and the Src family PTKs Lck and Fyn as enzymes capable of phosphorylating these sites in vivo and in vitro. Both Tyr-131 and Tyr-132 are located next to the catalytic pocket of LMPTP, and especially, Tyr-131 seems to be important for the activity of LMPTP. Phosphorylation of Tyr-131 or Tyr-132, particularly the former, caused an increase in the activity of LMPTP.

SIGNOR-251150

P06239

P03372

1

phosphorylation

up-regulates

0.382

On the basis of these data and other reports describing the structure and activity of y537 mutations, as well as knowledge of the three-dimensional structure of the her ligand binding domain, we propose an alternate model wherein y537f mutation favors an open pocket conformation, affecting the estrogen binding kinetics and stability of the hormone-bound, transcriptionally active closed pocket conformation.

SIGNOR-55853

P05771

Q06187

1

phosphorylation

down-regulates activity

0.382

We provide direct evidence that PKCbeta acts as a feedback loop inhibitor of Btk activation. Inhibition of PKCbeta results in a dramatic increase in B-cell receptor (BCR)-mediated Ca2+ signaling. We identified a highly conserved PKCbeta serine phosphorylation site in a short linker within the Tec homology domain of Btk. Mutation of this phosphorylation site led to enhanced tyrosine phosphorylation and membrane association of Btk, and augmented BCR and FcepsilonRI-mediated signaling in B and mast cells, respectively. | This deductive analysis indicated that PKCbeta phosphorylates S180 in the region bisecting the Btk motif (BM) and the PRR of the TH domain.

SIGNOR-249110

P49841

O00327

1

phosphorylation

down-regulates

0.382

Gsk3beta phosphorylates bmal1 specifically on ser 17 and thr 21 and primes it for ubiquitylation. In the absence of gsk3beta-mediated phosphorylation, bmal1 becomes stabilized and bmal1 dependent circadian gene expression is dampened.

SIGNOR-162786

Q06187

P40763

1

phosphorylation

down-regulates activity

0.382

Phosphorylation of STAT-3 by BTK may also alter the conformation of STAT-3 in such a way as to make it inaccessible as a substrate of activating kinases such as JAK3.|The ability of BTK to negatively regulate STAT-3 activity suggests several possible models for a mechanism of BTK action.

SIGNOR-279011

P49715

Q06945

1

transcriptional regulation

down-regulates

0.382

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

SIGNOR-255675

P60484

P10636

1

dephosphorylation

up-regulates activity

0.382

Reduced phosphorylation of PTEN can dramatically increase tau phosphorylation and impair the ability of tau to bind to microtubules .

SIGNOR-277079

P24941

Q05209

1

phosphorylation

down-regulates activity

0.382

In the present study, we found that S19 site phosphorylation of PTPN12 by CDK2 discharged its antitumor activity by down-regulation of its inhibitory role in cell migration, but not affecting its other regulatory functions.

SIGNOR-277366

Q9Y5B0

P30291

1

dephosphorylation

up-regulates activity

0.382

At mitosis exit, Fcp1 promoted inhibitory Cdk1 phosphorylation by dephosphorylating Wee1, and ubiquitin dependent cyclin B degradation by dephosphorylating Cdc20 and USP44.|This lead us to hypothesize that, during prolonged mitosis in AMCDs treated cancer cells, progressive Fcp1 induced Wee1 reactivation might lead to progressive loss of Cdk1 activity that weakens the SAC to a point in which the mitotic state could not be sustained .

SIGNOR-277142

Q9UBE8

P46531

1

phosphorylation

down-regulates

0.382

Nlk-phosphorylated notch1icd is impaired in its ability to form a transcriptionally_ active_ ternary_ complex.

SIGNOR-163697

P23467

P28482

1

dephosphorylation

down-regulates

0.382

Expression of rptp-beta inhibits both mek1/2 and erk1/2 phosphorylation.

SIGNOR-173000

Q5VWQ8

O75460

1

binding

up-regulates activity

0.382

DAB2IP binds IRE1α, and was shown to be required for activation of this signaling cascade in endothelial cells. IRE1α can trigger pro-apoptotic JNK signaling through recruitment of the TRAF2–ASK1 complex. DAB2IP facilitates IRE1α activation, and participates in a signaling complex required to induce TRAF2-dependent ASK1 activation and JNK phosphorylation.

SIGNOR-254749

Q9BXH1

Q16611

1

binding

up-regulates

0.382

Bim, and puma bind with high affinity to all pro-survival proteins

SIGNOR-196929

Q9BXM7

P99999

1

null

down-regulates quantity

0.382

There is a strong cyto-protective role of PINK1 in maintaining mitochondrial homeostasis via different mechanisms. Overexpression of wild-type PINK1 in SH-SY5Y neuroblastoma cells stabilizes respiring mitochondrial networks through various mechanisms that include maintaining mitochondrial membrane potential, reducing basal and neurotoxin-induced ROS, suppression of cytochrome c release, reversal of toxin-induced fission, and suppression of autophagy

SIGNOR-249704

A0PJZ3

P46531

1

binding

up-regulates

0.382

Recently, we have shown (28) that two members of the human glycosyltransferase 8 family (gt8) (29), gxylt1 and gxylt2 (glucoside-xylosyltransferase 1/2), are able to transfer the first alfa1,3-linked xylose to o-glucosylated mammalian notch egf repeats.

SIGNOR-177714

Q15139

Q15276

1

phosphorylation

up-regulates activity

0.382

PKD phosphorylates Rabaptin-5 at Ser407, and this controls alphavbeta3 and alpha5beta1 integrin and EGFR recycling.

SIGNOR-278192

O00358

P07202

1

transcriptional regulation

up-regulates quantity by expression

0.382

TSH regulates TPO expression through the cAMP pathway and acts with thyroid-specific transcription factors such as TTF-1, TTF-2 and Pax-8

SIGNOR-267279

O15105

Q8N5C8

1

binding

up-regulates

0.382

The formation of smad7-tab2 and smad7-tab3 complexes resulted in the suppression of tnf signaling.

SIGNOR-153920

Q9NXV6

P04637

1

binding

up-regulates

0.382

In the nucleoplasm, carf interacts with p53 and enhances its function.

SIGNOR-147360

P28482

P27708

1

phosphorylation

up-regulates

0.382

Cad is a multifunctional protein that initiates and regulates mammalian de novo pyrimidine biosynthesis. The activation of the pathway required for cell proliferation is a consequence of the phosphorylation of cad thr-456 by mitogen-activated protein (map) kinase.Activated map kinase (erk1/2), the enzyme responsible for the phosphorylation of thr-456, was also present in larger amounts in the nucleus than the cytosol

SIGNOR-137171

P27448

Q92974

1

phosphorylation

up-regulates activity

0.382

Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser151 This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules.

SIGNOR-277368

P00533

P0DP25

1

phosphorylation

down-regulates

0.382

Phosphorylation of calmodulin by the epidermal-growth-factor-receptor tyrosine kinase. Phosphorylated calmodulin does not exhibit the characteristic ca2+ shift normally observed with calmodulin in electrophoretic gels, an observation that is consistent with this modification affecting the biological activity of the molecule.

SIGNOR-266335

O95747

Q13153

1

phosphorylation

down-regulates activity

0.382

OSR1 phosphorylated threonine 84 in the N-terminal regulatory domain of PAK1. phosphorylation of PAK1 by OSR1 desensitizes PAK1 to activation by small G proteins, providing a modulatory input to PAK1 activity.

SIGNOR-250210

P17252

P06730

1

phosphorylation

up-regulates

0.382

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

SIGNOR-248945

P49354

P01116

1

null

up-regulates activity

0.382

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242559

Q13976

P31645

1

phosphorylation

up-regulates

0.382

These results are consistent with the hypothesis that pkg phosphorylates hsert at thr-276 and increases its activity by modifying the substrate permeation pathway formed, in part, by tm5.

SIGNOR-158186

P45983

O75581

1

phosphorylation

up-regulates

0.382

We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription.

SIGNOR-169007

O75093

P35052

1

binding

up-regulates

0.382

Slit family proteins are functional ligands of glypican-1 in nervous tissue and suggest that their interactions may be critical for certain stages of central nervous system histogenesis.

SIGNOR-68327

P53350

P33981

1

phosphorylation

up-regulates activity

0.381

Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. Plk1 Targets Mps1 Autophosphorylation Sites In Vitro

SIGNOR-276199

Q9UMX1

Q8NEA6

1

binding

down-regulates

0.381

These data indicate that the inhibition of glis3-mediated transactivation by sufu appears to rely on the interaction with glis3 through the ygh motif and is not related to an effect on the general transcriptional machinery

SIGNOR-173573

P24941

P38432

1

phosphorylation

up-regulates

0.381

In particular, we have recently found that the cdk2/cyclin e complex can phosphorylate coilin in vitro . there is but a single consensus cdk2/cyclin e phosphorylation site in coilin, located at serine 184. when serine 184 was mutated to an alanine (s184a), mimicking a dephosphorylated state, a nucleolar mislocalization similar to that of gfp-coilin(1_248) was observed

SIGNOR-84949

P63092

O15169

1

binding

up-regulates

0.381

We show that pge2 stimulates colon cancer cell growth through its heterotrimeric guanine nucleotide-binding protein (g protein) coupled receptor, ep2, by a signaling route that involves the activation of phosphoinositide 3-kinase and the protein kinase akt by free g protein bg subunits and the direct association of the g protein as subunit with the regulator of g protein signaling (rgs) domain of axin.

SIGNOR-141789

P56545

P12830

1

transcriptional regulation

down-regulates quantity by repression

0.381

Overexpression of the CtBP2 protein enhanced the repression activity of the E-cadherin promoter in a dose-dependent manner, whereas overexpression of ataxin-1 increased the activity of the E-cadherin promoter in a dose-dependent manner

SIGNOR-261578

P11309

P10275

1

phosphorylation

up-regulates activity

0.381

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-277575

Q8NI17

O60674

1

binding

up-regulates

0.381

Il-31 can activate janus kinase (jak) 1 and jak2 signaling molecules after binding to its receptor complex.

SIGNOR-161430

Q7Z6M2

P67809

1

binding

down-regulates quantity by destabilization

0.381

Here we identify FBX33 as a component of an SCF E3-ubiquitin ligase that targets the multifunctional regulator Y-box binding protein 1 (YB-1)/dbpB/p50 for polyubiquitination and destruction by the proteasome. By targeting YB-1 for proteasomal degradation, FBX33 negatively interferes with YB-1 mediated functions. FBX33 recruits Skp-1/Cul1 to YB-1

SIGNOR-271604

P07948

Q92918

1

phosphorylation

up-regulates activity

0.381

BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.

SIGNOR-251403

P35452

Q9ULX9

1

binding

down-regulates activity

0.381

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221884

Q9NV58

P41180

1

ubiquitination

down-regulates quantity by destabilization

0.381

Coexpression with dorfin decreased the amount of total CaR protein and increased CaR ubiquitination, whereas a dominant negative fragment of dorfin had opposite effects. dorfin-mediated proteasomal degradation of immature CaR occurs from the endoplasmic reticulum. Because endogenous CaR in Madin-Darby canine kidney cells is also subject to degradation from the endoplasmic reticulum, dorfin-mediated ubiquitination may contribute to a general mechanism for CaR quality control during biosynthesis.

SIGNOR-271456

Q92793

P28069

1

binding

up-regulates activity

0.381

We and others have recently shown that CBP can constitutively bind to Pit-1 and synergistically activate transcription of promoters containing Pit-1 DNA-binding sites.

SIGNOR-267204

Q9Y6E0

Q15208

1

phosphorylation

up-regulates

0.381

Ndr1/ndr2 protein kinase is activated by phosphorylation on the activation loop phosphorylation site ser281/ser282 and the hydrophobic motif phosphorylation site thr444/thr442. Autophosphorylation of ndr is responsible for phosphorylation on ser281/ser282, whereas thr444/thr442 is targeted by an upstream kinase. Here we show that mst3, a mammalian ste20-like protein kinase, is able to phosphorylate ndr protein kinase at thr444/thr442. In vitro, mst3 selectively phosphorylated thr442 of ndr2, resulting in a 10-fold stimulation of ndr activity.

SIGNOR-142467

Q9H0M0

Q9BT67

1

ubiquitination

down-regulates quantity

0.381

Accordingly, the ubiquitination assays were performed and the results revealed that knockdown of WWP1 reduced the ubiquitination of NDFIP1 in HuCCT1 and vice versa in HCCC-9810 and RBE (Fig. 7E).|In addition, we found that WWP1 could reduce the protein level of NDFIP1 via ubiquitination.

SIGNOR-278796

Q9Y243

Q96ST2

1

phosphorylation

up-regulates activity

0.381

The data presented in this report confirmed the differential phosphorylation of IWS1 at Ser720/Thr721 by Akt3 and Akt1 and showed that its phosphorylation at this site is required for the recruitment of SetD2 to the Spt6-IWS1-Aly/REF complex.

SIGNOR-273496

P49841

Q9UBN7

1

phosphorylation

up-regulates activity

0.381

GSK3beta was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3beta resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3beta phosphorylation site in HDAC6.|This suggests that GSK3\u03b2 may directly phosphorylate HDAC6 at this site, although further work with purified proteins is needed to determine whether this is the case.|The fact that HDAC6 is the predominant cytoplasmic deacetylase in neurons suggests that GSK3beta dependent phosphorylation may enhance HDAC6 activity, resulting in a decrease in acetylation of tubulin and an inhibition of both mitochondrial motility and the transport of other kinesin-1 dependent cargoes.

SIGNOR-278941

Q16620

P06241

1

binding

up-regulates

0.381

All these data suggest the involvement of fyn in the neurotrophin signal transduction pathways downstream of trkb. We investigated whether fyn is involved in the trk-dependent signal transduction pathways of neurotrophin. The fyn-src homology domain 2 (sh2) was observed to associate in vitro with the intracellular domain of trkb (icd-trkb).

SIGNOR-58424

P28482

P09917

1

phosphorylation

up-regulates activity

0.381

Intriguingly, a significant difference in the potency of nonredox-type inhibitors (but not of BWA4C) was determined between wild-type 5-LO and the mutant S271A/S663A-5-LO (lacking phosphorylation sites for ERK1/2 and MAPKAPK-2) in HeLa cells. Collectively, our data suggest that compared with Ca2+-mediated 5-LO product formation, enzyme activation involving 5-LO phosphorylation events specifically and strongly alters the susceptibility of 5-LO toward nonredox-type inhibitors in intact cells.

SIGNOR-264409

Q9NQS1

Q13315

2

binding

up-regulates activity

0.381

These data suggest that Aven overexpression can activate ATM and that Aven phosphorylation in a positive feedback loop enforces Aven activity, making it a more potent ATM activator.

SIGNOR-262638

Q86Y01

Q09472

1

binding

up-regulates

0.381

We found that a significant fraction of dtx1 proteins were localized in the nucleus and physically interacted with the transcriptional coactivator p300.

SIGNOR-110629

Q9BYH8

Q16552

1

transcriptional regulation

up-regulates quantity by expression

0.381

In cooperation with RORγt and RORα, IκBζ enhances Il17a expression by binding directly to the regulatory region of the Il17a gene.

SIGNOR-266210

Q13315

Q9NQS1

2

phosphorylation

up-regulates activity

0.381

Aven is also a substrate of the ATM kinase. Mutation of ATM-mediated phosphorylation sites on Aven reduced its ability to activate ATM, suggesting that Aven activation of ATM after DNA damage is enhanced by ATM-mediated Aven phosphorylation. We found that mutating S135 and S308 sites to Alanine largely dampened Aven’s phosphorylation by ATM (though some phosphorylation remained, due to either a contaminating kinase or an unidentified ATM phosphorylation site).

SIGNOR-262636

P36897

P27986

1

binding

up-regulates

0.381

These studies revealed that PI 3-kinase is associated in vivo with both TGF-_ receptor subtypes and that TGF-_1 stimulation enhances PI 3-kinase activity associated with type I TGF-_ receptor in hASM cells.

SIGNOR-227525

P05129

P30086

1

phosphorylation

up-regulates activity

0.381

Here we report that one mechanism involves dissociation of Raf kinase inhibitory protein (RKIP) from Raf-1. Classic and atypical but not novel PKC isoforms phosphorylate RKIP at serine 153 (Ser-153). RKIP Ser-153 phosphorylation by PKC either in vitro or in response to 12-O-tetradecanoylphorbol-13-acetate or epidermal growth factor causes release of RKIP from Raf-1, whereas mutant RKIP (S153V or S153E) remains bound. I

SIGNOR-249190

P0C2W1

Q96IZ0

1

binding

down-regulates quantity by destabilization

0.381

Fbxo45 interacts with Par-4 in the cytoplasm and mediates its ubiquitylation and proteasomal degradation. Fbxo45 silencing results in stabilization of Par-4 with increased apoptosis.Fbxo45 forms an atypical ubiquitin ligase complex that contains Skp1 and the Ring-finger protein PAM (protein-associated with myc) also known as MYCBP2 (myc-binding protein 2).

SIGNOR-272223

O14965

Q9NRM7

1

phosphorylation

up-regulates

0.38

On the basis of these observations, we conclude that s83 of lats2 is a phosphorylation target of aurora-a and this phosphorylation plays a role of the centrosomal localization of lats2.

SIGNOR-124830

O15111

O75925

1

phosphorylation

up-regulates activity

0.38

In addition, we show that IKKalpha is associated with PIAS1 and mediates the S90 phosphorylation of PIAS1.|Mutational studies indicate that Ser90 phosphorylation is required for PIAS1 to repress transcription.

SIGNOR-278926

Q96A56

P60520

1

binding

up-regulates

0.38

In this work, we show that tp53inp1 is also able to interact with atg8-family proteins and to induce autophagy-dependent cell death. mammalian cells contain multiple atg8 orthologs belonging to three subfamilies: microtubule-associated protein 1 light chain 3, -aminobutyric acid receptor-associated protein (gabarap) and -aminobutyric acid receptor-associated protein like 2 (gabarapl2).

SIGNOR-196667

Q9NWZ3

P14598

1

phosphorylation

up-regulates

0.38

Phosphorylation of the cytosolic factor p47phox is essential for activation of the nadph oxidase.We found that thr133, ser288 and thr356, targets for irak-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after lps stimulation. We conclude that irak-4 phosphorylates p47phox and regulates nadph oxidase activation after lps stimulation.

SIGNOR-152027

Q6IQ23

Q5EBL8

1

binding

up-regulates activity

0.38

Using cell biological and biochemical methods, we now show that ADAM10 is docked to junctions by its transmembrane partner Tspan33, whose cytoplasmic C terminus binds to the WW domain of PLEKHA7 in the presence of PDZD11. The PLEKHA7-PDZD11 Complex Clusters ADAM10 at Junctions through Tspan33

SIGNOR-261253

P04150

Q03135

1

binding

up-regulates

0.38

He mGR appears to reside in caveolae and its association with caveolin-1 (Cav-1) was clearly detected in two of the four cell lines investigated using double recognition proximity ligation assay.

SIGNOR-251683

P01222

Q92911

1

transcriptional regulation

up-regulates quantity by expression

0.38

Iâ€“ uptake is stimulated by TSH, the master hormone for thyroid gland regulation. TSH stimulation results, at least in part, from the cAMP-mediated increase in NIS biosynthesis. TSH not only stimulates NIS transcription and biosynthesis but is also required for modulating the NIS phosphorylation pattern, maintaining its half-life, and retaining NIS at the thyrocyte plasma membrane

SIGNOR-251995

P27361

P53805

1

phosphorylation

up-regulates activity

0.38

Consensus phosphorylation sites for p42/44 MAPK and GSK-3 are present in the SP repeat of MCIP1 at serine 112 and serine 108, respectively |Several endogenous proteins are capable of inhibiting the catalytic activity of calcineurin. Modulatory calcineurin interacting protein 1 (MCIP1) is unique among these proteins on the basis of its pattern of expression and its function in a negative feedback loop to regulate calcineurin activity. Here we show that MCIP1 can be phosphorylated by MAPK and glycogen synthase kinase-3 and that phosphorylated MCIP1 is a substrate for calcineurin.

SIGNOR-249478

Q96GD4

Q01860

1

phosphorylation

down-regulates activity

0.38

Aurkb phosphorylates Oct4(S229) during G2/M phase, leading to the dissociation of Oct4 from chromatin, whereas PP1 binds Oct4 and dephosphorylates Oct4(S229) during M/G1 transition, which resets Oct4-driven transcription for pluripotency and the cell cycle.

SIGNOR-279592

P18031

Q16620

1

dephosphorylation

down-regulates activity

0.38

Collectively, these data establish a direct enzyme-substrate interaction between PTP1B and phosphorylated Y705/706 (p-Y705/706) TRKB, the critical autophosphorylation sites that mediate BDNF-induced signaling.| Therefore, the data are consistent with a role of PTP1B as an inhibitor of BDNF/TRKB signaling

SIGNOR-264554

P17252

Q9HBA0

1

phosphorylation

up-regulates activity

0.38

We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.

SIGNOR-260882

P00519

P18206

1

phosphorylation

up-regulates activity

0.38

Abl is the tyrosine kinase that phosphorylates vinculin Y822.|Finally we show that Abl inhibition prevents vinculin actions in cadherin containing complexes, resulting in defects in cell stiffening.

SIGNOR-278464

P14091

P01023

1

cleavage

down-regulates quantity by destabilization

0.38

Disruption of structural and functional integrity of alpha 2-macroglobulin by cathepsin E|Analysis of the N-terminal amino-acid sequences of these proteins revealed that alpha 2M was selectively cleaved at the Phe811-Leu812 bond in about 100mer downstream of the bait region.

SIGNOR-266977

Q8IVH8

Q04759

1

phosphorylation

up-regulates

0.38

We report that the kinase glk (map4k3) directly activated pkc-? During tcr signaling.

SIGNOR-176744

P12931

Q16832

1

phosphorylation

up-regulates

0.38

Here, using baculoviral co-expression of the ddr2 cytosolic domain and src, we show that src targets three tyrosine residues (tyr-736, tyr-740, and tyr-741) in the activation loop of ddr2 for phosphorylation. This phosphorylation by src stimulates ddr2 cis-autophosphorylation of additional tyrosine residues.

SIGNOR-140767

P18031

Q13480

1

dephosphorylation

down-regulates activity

0.38

Since Gab1 is negatively regulated by PTP1B, a part of the retinal neuroprotective effect we have observed previously in PTP1B deficient mice could be contributed by Gab1 as well.|The results indicate that PTP1B completely dephosphorylated Gab1 and the mutant protein failed to dephosphorylate Gab1 (Figure\u00a0 xref C).

SIGNOR-276965

Q05513

Q96RI1

1

phosphorylation

up-regulates

0.38

The effect of fic1 on fxr phosphorylation and nuclear localization and its effects on bsep promoter activity could be blocked with protein kinase c zeta (pkc zeta) inhibitors (pseudosubstrate or small interfering rna silencing). Recombinant pkc zeta directly phosphorylated immunoprecipitated fxr. The mutation of threonine 442 of fxr to alanine yielded a dominant negative protein,

SIGNOR-179771

P06241

Q13322

1

phosphorylation

down-regulates

0.38

Grb10 tyrosine phosphorylation was stimulated by expression of constitutively active src or fyn in cells and by incubation with purified src or fyn in vitro. The insulin stimulated or src/fyn-mediated tyrosine phosphorylation in vivo was significantly reduced when grb10 tyrosine 67 was changed to glycine. This mutant form of grb10 bound with higher affinity to the ir in cells than that of the wild-type protein, suggesting that tyrosine phosphorylation of grb10 may normally negatively regulate its binding to the ir.

SIGNOR-78702

Q6ZNJ1

Q96N67

1

binding

up-regulates activity

0.38

In summary, from 129 binding partners of Nbeal2 identified by mass spectrometry, we have confirmed the interaction of 3, Dock7, Sec16a, and Vac14, by different biochemical and cellular approaches|Given the significant reduction of Dock7 levels and its altered localization in Nbeal2−/− platelets, we postulated that this canonical signaling pathway may be disrupted and set out to test this using control and Nbeal2−/− platelets.

SIGNOR-261891

P28482

Q01860

1

phosphorylation

down-regulates

0.38

We demonstrate that oct4a interacts with erk1/2 by using both in vitro gst pulldown and in vivo co-immunoprecipitation assays. Ms analysis identified phosphorylation of oct4a at ser-111. / serine 111 phosphorylation regulates oct4a protein subcellular distribution and degradation.

SIGNOR-192097

Q9H4B4

Q16143

1

phosphorylation

down-regulates activity

0.38

Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation.

SIGNOR-189057