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
P0C2W1	O95863	1	binding	down-regulates quantity by destabilization	0.357	One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively.	SIGNOR-272181
Q13976	P19429	1	phosphorylation	up-regulates activity	0.357	Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.	SIGNOR-134644
P68400	P07910	1	phosphorylation	down-regulates activity	0.357	In contrast, hnRNP-C1 that was also modified at the CK1alpha phosphorylation sites exhibited a 14-500-fold decrease in binding affinity, demonstrating that CK1alpha-mediated phosphorylation modulates the mRNA binding ability of hnRNP-C.	SIGNOR-133540
Q92913	Q15858	1	binding	down-regulates activity	0.357	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-253423
P51812	P11362	1	phosphorylation	down-regulates quantity	0.357	Both in vitro and in vivo experiments confirmed the interaction and we show that phosphorylated RSK2 binds to and phosphorylates serine 789 in the C-terminal tail of FGFR1.prevention of FGFR1 phosphorylation by inhibition of RSK2 activity or mutation of serine 789 to alanine reduced FGFR1 endocytosis and ubiquitination explaining mechanistically the prolonged signaling activity.	SIGNOR-276599
P51452	P00533	1	dephosphorylation	down-regulates activity	0.357	We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR.	SIGNOR-248532
Q16539	P26651	1	phosphorylation	down-regulates activity	0.357	TTP appears to be a p38Î±/Î² MAPK target and pretreating skeletal muscle with a p38Î±/Î² MAPK inhibitor reduces TTP phosphorylation.	SIGNOR-253596
Q18PE1	P46108	1	binding	up-regulates activity	0.357	Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7.	SIGNOR-273847
Q9NYY3	Q9Y4G8	1	phosphorylation	up-regulates activity	0.357	Here, we report that Plk2 phosphorylates a quartet of Ras and Rap regulators : SynGAP, PDZGEF1, RasGRF1 and SPAR, resulting in powerful bidirectional control over Rap and Ras activity.\|Thus, Plk2 was sufficient to promote the activities of both SynGAP and PDZGEF1 in mammalian cells.	SIGNOR-280066
Q06587	Q13642	1	binding	up-regulates	0.357	The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo	SIGNOR-123150
Q9HAZ1	Q07955	1	phosphorylation	up-regulates activity	0.357	In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.	SIGNOR-273860
P17252	P49841	1	phosphorylation	down-regulates	0.357	Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka).	SIGNOR-188581
Q86UW7	Q16623	1	binding	up-regulates activity	0.357	CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1	SIGNOR-264337
O60729	Q13309	1	dephosphorylation	down-regulates quantity by destabilization	0.357	The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1).	SIGNOR-248333
Q09472	P52292	1	acetylation	up-regulates	0.357	Ampk triggered the acetylation of importin alpha1 on lys(22), a process dependent on the acetylase activity of p300	SIGNOR-128625
O15530	Q13153	1	phosphorylation	up-regulates activity	0.357	P21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). We identify threonine 423, a conserved threonine in the activation loop of kinase subdomain VIII, as the PDK1 phosphorylation site on PAK1.	SIGNOR-250267
P07948	Q9Y6K9	1	phosphorylation	down-regulates activity	0.357	Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.	SIGNOR-276369
Q9P2B4	Q14247	1	binding	up-regulates activity	0.357	CTTNBP2NL interacts with cortactin and targets cortactin to stress fibers.	SIGNOR-261695
Q92949	Q5JVL4	1	transcriptional regulation	up-regulates quantity by expression	0.356	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266934
Q05D32	Q8N165	1	dephosphorylation	up-regulates quantity by stabilization	0.356	We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).	SIGNOR-273773
P01106	P22626	1	transcriptional regulation	up-regulates quantity by expression	0.356	We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2,	SIGNOR-268691
P43405	Q8N6F7	1	phosphorylation	up-regulates activity	0.356	Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.	SIGNOR-273570
Q9Y2R2	Q96P20	1	dephosphorylation	up-regulates activity	0.356	Further, this explains how loss of PTPN22 and subsequent enhanced NLRP3 phosphorylation mediate a decrease in NLRP3 inflammasome activation.\|Upon NLRP3 activation, PTPN22 dephosphorylates NLRP3 and thereby protects it from degradation, allowing robust inflammasome activity (summarized in Fig.S6).	SIGNOR-277056
P62136	Q00987	1	dephosphorylation	up-regulates quantity by stabilization	0.356	Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.	SIGNOR-248566
P31749	Q13188	1	phosphorylation	down-regulates	0.356	We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2.	SIGNOR-163533
Q15139	O75628	1	phosphorylation	up-regulates activity	0.356	We found that activation of protein kinase D1, a protein kinase downstream of α(1)-adrenergic signaling, leads to direct phosphorylation of Rem1 at Ser18. This results in an increase of the channel activity and plasma membrane expression observed by using a combination of electrophysiology, live cell confocal microscopy, and immunohistochemistry in heterologous expression system and neonatal cardiomyocytes.	SIGNOR-273832
Q13237	Q12778	1	phosphorylation	up-regulates activity	0.356	Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2.	SIGNOR-279564
Q9UNE7	P17542	1	ubiquitination	down-regulates quantity by destabilization	0.356	Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. CHIP promoted Tal1 degradation with both chaperone binding and ubiquitin ligase activities, which are mediated by its TPR domain and U box, respectively.	SIGNOR-271393
Q9UBN7	Q01130	1	deacetylation	up-regulates	0.356	Our data support a model in which hdac6 has a key role in the maintenance of srsf2 protein level by inhibiting tip60_mediated acetylation and proteasomal degradation.	SIGNOR-170590
Q13616	Q9Y4X5	1	binding	up-regulates activity	0.356	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-268844
P31431	O14640	1	binding	up-regulates	0.356	Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.	SIGNOR-199632
P11802	P43694	1	phosphorylation	up-regulates activity	0.356	In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).\|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.	SIGNOR-279148
O14920	P08151	1	phosphorylation	up-regulates activity	0.356	Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.\|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.	SIGNOR-279194
Q01664	P08047	1	binding	up-regulates activity	0.356	We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads.	SIGNOR-226593
P01106	P17480	1	transcriptional regulation	up-regulates quantity by expression	0.356	MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation\|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.	SIGNOR-269644
Q00535	Q13794	1	phosphorylation	down-regulates	0.356	We show that noxa is phosphorylated on a serine residue (s(13)) in the presence of glucose. Phosphorylation promotes its cytosolic sequestration and suppresses its apoptotic function. We identify cdk5 as the noxa kinase	SIGNOR-170357
Q9UQ88	O95238	1	phosphorylation	down-regulates quantity by destabilization	0.356	In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues\|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.\|	SIGNOR-273022
Q00535	Q8IV63	1	phosphorylation	up-regulates activity	0.356	Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding\|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation\|	SIGNOR-275544
Q9UNE7	O15519	1	ubiquitination	down-regulates quantity by destabilization	0.356	Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.\|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.	SIGNOR-278783
Q08211	P52948	1	binding	up-regulates activity	0.356	Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription.	SIGNOR-260954
Q00987	O15055	1	polyubiquitination	down-regulates quantity by destabilization	0.356	We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation.	SIGNOR-277421
P23443	Q92519	1	phosphorylation	down-regulates quantity by destabilization	0.356	Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.	SIGNOR-275433
P21918	P09471	1	binding	up-regulates activity	0.356	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-257244
P34947	Q9UQL6	1	phosphorylation	down-regulates activity	0.356	GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.	SIGNOR-279045
O75592	P49815	1	ubiquitination	down-regulates quantity by destabilization	0.356	We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain.	SIGNOR-278704
P06493	O95251	1	phosphorylation	up-regulates	0.355	Here, we show that the interaction between plk1 and hbo1 is mitosis-specific and that plk1 phosphorylates hbo1 on ser-57 in vitro and in vivo. During mitosis, cdk1 phosphorylates hbo1 on thr-85/88, creating a docking site for plk1 to be recruited. Significantly, the overexpression of hbo1 mutated at the plk1 phosphorylation site (s57a) leads to cell-cycle arrest in the g1/s phase, inhibition of chromatin loading of the minichromosome maintenance (mcm) complex, and a reduced dna replication rate.	SIGNOR-160747
Q13490	P57078	1	polyubiquitination	up-regulates activity	0.355	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.	SIGNOR-272708
P06493	P68400	2	phosphorylation	up-regulates	0.355	Four residues within this domain, thr-344, thr-360, ser-362, and ser-370, conform to the minimal consensus sequence for p34cdc2 phosphorylationthe high stoichiometry of phosphorylation suggests that phosphorylation could regulate functional properties of ckii and that it could in some way participate in the burst of phosphorylation that accompanies the activation of p34graphic at the ggraphic-m transition	SIGNOR-29525
P68400	P06493	2	phosphorylation	up-regulates	0.355	Additionally, transfection of cdc2 with a mutation at ser(39) to ala, which is the ck2 phosphorylation site, partially inhibits cell cycle progression in g(1) to g(2) phase following 6-tg treatment.	SIGNOR-134846
Q13489	P57078	1	polyubiquitination	up-regulates activity	0.355	CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.	SIGNOR-272709
P31749	P29317	1	phosphorylation	up-regulates activity	0.355	As non-canonical EphA2 activation requires phosphorylation of EphA2 at serine 897 by pAkt (Fig.\u00a02b), we sought to determine the effect of PTEN-mediated Akt regulation on invasion.	SIGNOR-279787
Q6ZNA4	P29590	1	polyubiquitination	down-regulates quantity by destabilization	0.355	Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.	SIGNOR-272883
P23469	Q14721	1	dephosphorylation	down-regulates activity	0.355	Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon	SIGNOR-248450
P06493	O94761	1	phosphorylation	up-regulates activity	0.355	During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs.	SIGNOR-277375
P12931	P51812	1	phosphorylation	up-regulates	0.355	Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway.	SIGNOR-160052
Q15139	Q9BST9	1	phosphorylation	up-regulates activity	0.355	Here, we show that rhotekin, an effector of RhoA GTPase, is a novel substrate of PKD. We identified Ser-435 in rhotekin as the potential site targeted by PKD in vivo. Expression of a phosphomimetic S435E rhotekin mutant resulted in an increase of endogenous active RhoA GTPase levels. Phosphorylation of rhotekin by PKD2 modulates the anchoring of the RhoA in the plasma membrane.	SIGNOR-275511
P08631	Q13444	1	phosphorylation	up-regulates	0.355	Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.	SIGNOR-112919
P04150	P06239	1	binding	up-regulates	0.355	The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation.	SIGNOR-251685
P24723	Q15139	1	phosphorylation	up-regulates	0.355	These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.	SIGNOR-66734
Q9H1C0	Q03113	1	binding	up-regulates activity	0.355	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-257205
P23443	P78362	1	phosphorylation	up-regulates activity	0.355	Altogether, these results identify S6K1-phosphorylated SRPK2 as an essential mediator of IGF1-stimulated SG formation in hPDAC cells.\|The nodes of the core SG network are known to contribute to SG formation to varying degrees and it is possible that S6K1-stimulated SRPK2 may impact their contribution; this is consistent with the predicted model whereby SG assembly is subject to regulation by positive and negative cooperativity of extrinsic factors with the core network interactions (14).	SIGNOR-280121
Q15208	Q9BX46	1	phosphorylation	up-regulates activity	0.355	Phosphorylation of Rbm24 by Stk38 is crucial for the maintenance of cardiac sarcomeric gene expression in cardiac cells.\|These results indicated that Stk38 increases Rbm24 protein stability probably by interfering with the ubiquitin-proteasome protein degradation pathway.	SIGNOR-278291
Q13315	Q9NY61	1	phosphorylation	up-regulates quantity by stabilization	0.355	The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. \|DNA damage stabilizes Che-1 protein\|In addition, substitution of Che-1 Ser187 with an alanine (Che-1S187A) prevented Che-1 phosphorylation by ATM (Figure 2F), supporting this residue as an ATM-target site.	SIGNOR-264415
P45984	P12931	1	phosphorylation	up-regulates activity	0.355	Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).\|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.	SIGNOR-279221
Q86X55	P40925	1	acetylation	down-regulates activity	0.355	Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer\|Arginine methylation at R248 negatively regulates MDH1 activity\|PRMT4/CARM1 methylates MDH1 at R248 and inhibits its dimerization	SIGNOR-267639
Q04759	P22681	1	phosphorylation	up-regulates activity	0.355	PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins	SIGNOR-274144
Q96BR1	Q13045	1	phosphorylation	up-regulates	0.355	Here we show that flii is an in vivo substrate of cisk that functions downstream of pi 3-kinase. Cisk can associate with flii and phosphorylate flii at residues ser(436) and thr(818).We demonstrate here that cisk can enhance er transcription, which is dependent on its kinase activity, and mutation of cisk phosphorylation sites on flii attenuates its activity as an er co-activator.	SIGNOR-184688
Q05086	P20618	1	ubiquitination	down-regulates quantity by destabilization	0.355	Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.	SIGNOR-265131
P50570	O00159	1	binding	up-regulates	0.355	Dynamin bind directly to the sh3 domain of myo1e / an intriguing possibility is that binding of dynamin and synaptojanin to myo1e tail may activate motor activity since it has been demonstrated that myo1e atpase activity is autoinhibited by its sh3 domain	SIGNOR-152910
Q05655	Q15080	1	phosphorylation	up-regulates activity	0.355	P40(phox) is phosphorylated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process.	SIGNOR-249012
P06493	O15287	1	phosphorylation	up-regulates	0.355	S387a mutant abolished fancg fusion protein phosphorylation by cdc2.	SIGNOR-129061
P31749	Q8IYJ3	1	phosphorylation	down-regulates quantity	0.355	By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241. Phosphorylation did not alter the ability of JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo phosphorylation, JFC1 dissociates from the membrane, promoting JFC1 redistribution to the cytosol.	SIGNOR-273540
Q9NWF9	Q8IUC6	1	ubiquitination	down-regulates quantity by destabilization	0.355	Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.	SIGNOR-271609
P49841	Q08050	1	phosphorylation	down-regulates quantity by destabilization	0.355	GSK3 phosphorylates FoxM1 on serine 474 which induces FoxM1 ubiquitination mediated by FBXW7.	SIGNOR-277208
Q7Z6J0	Q02779	1	binding	up-regulates	0.355	Taken together, these findings support a model in which apoptotic stimuli or posh overexpression induce direct association between posh and inactive mlks.	SIGNOR-97003
P06493	P23769	1	phosphorylation	down-regulates quantity by destabilization	0.355	GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).	SIGNOR-276884
P00519	O75496	1	phosphorylation	up-regulates activity	0.355	Taken together, suggests that c-Abl binds and phosphorylates geminin on Y150 in G2/M/early G1 phases.	SIGNOR-278505
Q9Y463	P46527	1	phosphorylation	up-regulates	0.355	Mirk phosphorylates p27 at ser-10, thus stabilizing p27 and blocking its nuclear export and degradation	SIGNOR-235805
Q02078	P12882	1	transcriptional regulation	up-regulates quantity by expression	0.355	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-238748
P28482	O94811	1	phosphorylation	down-regulates activity	0.354	Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.	SIGNOR-262928
P18031	P78337	1	dephosphorylation	down-regulates quantity by destabilization	0.354	PTP1B dephosphorylates PITX-1 at Y160, 175 and Y179.\|Through directly dephosphorylating PITX-1 at Y160, Y175 and Y179, PTP1B promoted proteasomal degradation of PITX-1, thus leaded in downregulating p120RasGAP and CRC cell survival.	SIGNOR-276973
P48729	P07910	1	phosphorylation	down-regulates	0.354	A kinase activity was identified in mouse liver that phosphorylates the acd of hnrnp-c at ser(240) and at two sites at ser(225)-ser(228). The kinase was purified and identified by tandem mass spectrometry as protein kinase ck1alpha (formerly casein kinase 1alpha).hnrnp-c1 that was also modified at the ck1alpha phosphorylation sites exhibited a 14-500-fold decrease in binding affinity, demonstrating that ck1alpha-mediated phosphorylation modulates the mrna binding ability of hnrnp-c.	SIGNOR-133528
P18031	P25963	1	dephosphorylation	down-regulates	0.354	Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha	SIGNOR-45004
P28482	P50616	1	phosphorylation	down-regulates	0.354	Tob is rapidly phosphorylated at ser 152, ser 154, and ser 164 by erk1 and erk2 upon growth-factor stimulation.	SIGNOR-88720
P53350	Q8IWB6	1	phosphorylation	down-regulates quantity by destabilization	0.354	We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.	SIGNOR-273529
Q13976	Q9Y613	1	phosphorylation	up-regulates	0.354	Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization	SIGNOR-123646
P53350	P18031	1	phosphorylation	up-regulates activity	0.354	Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.\|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.	SIGNOR-272990
P54821	Q9ULX9	1	binding	down-regulates activity	0.354	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-221890
P09874	Q9UGL1	1	relocalization	up-regulates activity	0.354	The mechanism of KDM5B recruitment is quite specific and requires the presence of nucleosomes containing histone variant MacroH2A1.1 and PARylation by PARP1.	SIGNOR-271574
Q9UIK4	Q8N122	1	phosphorylation	down-regulates activity	0.354	DAPK2 phosphorylates raptor in vitro on Ser721.	SIGNOR-278243
Q9Y243	O15119	1	phosphorylation	up-regulates activity	0.354	We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion.	SIGNOR-223534
P28482	Q15648	1	phosphorylation	up-regulates	0.354	We demonstrate that erk phosphorylates trap220/med1 in vivo at two specific sites: threonine 1032 and threonine 1457. importantly, we found that erk phosphorylation significantly increases the stability and half-life of trap220/med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription.	SIGNOR-142462
Q96BR1	P49840	1	phosphorylation	down-regulates activity	0.354	Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity\|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.\|The effect of SGK1 was mimicked by PKB and SGK3.	SIGNOR-249165
P31749	P07550	1	phosphorylation	down-regulates	0.354	Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation.	SIGNOR-252470
P06239	P24666	1	phosphorylation	up-regulates activity	0.354	In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation.	SIGNOR-251367
Q15262	Q9ULT6	1	dephosphorylation	up-regulates activity	0.354	We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.	SIGNOR-260110
P27361	P35228	1	phosphorylation	up-regulates	0.354	Erk phosphorylated inos on ser745. Mutation of ser745 to ala did not affect basal inos activity but eliminated inos phosphorylation and activation in response to b1r agonist.	SIGNOR-157711
Q13315	Q9UGP5	1	phosphorylation	up-regulates activity	0.354	We show that Polλ is efficiently phosphorylated by DNA-PKcs in vitro and predominantly by ATM after DSB induction with ionizing radiation (IR) in vivo. We identify threonine 204 (T204) as a main target for ATM/DNA-PKcs phosphorylation on human Polλ, and establish that its phosphorylation may facilitate the repair of a subset of IR-induced DSBs and the efficient Polλ-mediated gap-filling during NHEJ.	SIGNOR-273836
A1L390	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.354	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260585
P68400	Q15185	1	phosphorylation	up-regulates	0.354	Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.	SIGNOR-123594

P0C2W1

O95863

1

binding

down-regulates quantity by destabilization

0.357

One of the hallmarks of EMT is loss of E-cadherin and gain of N-cadherin expression, which are regulated by the core EMT-inducing transcription factors (EMT-TFs), such as Zeb1/2, Snai1/2 and Twist1. Here, we find that EMT-TFs can be dynamically degraded by an atypical ubiquitin E3 ligase complex Skp1-Pam-Fbxo45 (SPFFbxo45) through the ubiquitin proteasome system (UPS). The key step is recognition of EMT-TFs by Fbxo45 through its SPRY domain for Zeb2, or F-box domain for the other three EMT-TFs Snai1, Snai2 and Twist1, respectively.

SIGNOR-272181

Q13976

P19429

1

phosphorylation

up-regulates activity

0.357

Phosphorylation at ser 23/24 (e.g., by pka or pkg) results in reduction in myofilament ca2+ sensitivity and an increase in crossbridge cycling rate, leading to acceleration of relaxation and an increase in power output but a reduced economy of contraction. Conversely, phosphorylation at ser 43/45 (by pkc) is associated with reduced maximum ca2+-activated force and decreased crossbridge cycling rates, which are likely to reduce power output and delay relaxation, with an increased economy of contraction.

SIGNOR-134644

P68400

P07910

1

phosphorylation

down-regulates activity

0.357

In contrast, hnRNP-C1 that was also modified at the CK1alpha phosphorylation sites exhibited a 14-500-fold decrease in binding affinity, demonstrating that CK1alpha-mediated phosphorylation modulates the mRNA binding ability of hnRNP-C.

SIGNOR-133540

Q92913

Q15858

1

binding

down-regulates activity

0.357

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-253423

P51812

P11362

1

phosphorylation

down-regulates quantity

0.357

Both in vitro and in vivo experiments confirmed the interaction and we show that phosphorylated RSK2 binds to and phosphorylates serine 789 in the C-terminal tail of FGFR1.prevention of FGFR1 phosphorylation by inhibition of RSK2 activity or mutation of serine 789 to alanine reduced FGFR1 endocytosis and ubiquitination explaining mechanistically the prolonged signaling activity.

SIGNOR-276599

P51452

P00533

1

dephosphorylation

down-regulates activity

0.357

We found that EGF receptor (EGFR) was a direct substrate of VHR and that overexpression of VHR down-regulated EGFR phosphorylation, particularly at Tyr-992 residue. Expression of VHR inhibited the activation of phospholipase Cγ and protein kinase C, both downstream effectors of Tyr-992 phosphorylation of EGFR.

SIGNOR-248532

Q16539

P26651

1

phosphorylation

down-regulates activity

0.357

TTP appears to be a p38Î±/Î² MAPK target and pretreating skeletal muscle with a p38Î±/Î² MAPK inhibitor reduces TTP phosphorylation.

SIGNOR-253596

Q18PE1

P46108

1

binding

up-regulates activity

0.357

Here, we identify two tyrosine residues in Dok-7 that are phosphorylated by Agrin stimulation, and show that two proteins, Crk and Crk-L, are recruited to these phosphorylation sites in Dok-7.

SIGNOR-273847

Q9NYY3

Q9Y4G8

1

phosphorylation

up-regulates activity

0.357

Here, we report that Plk2 phosphorylates a quartet of Ras and Rap regulators : SynGAP, PDZGEF1, RasGRF1 and SPAR, resulting in powerful bidirectional control over Rap and Ras activity.|Thus, Plk2 was sufficient to promote the activities of both SynGAP and PDZGEF1 in mammalian cells.

SIGNOR-280066

Q06587

Q13642

1

binding

up-regulates

0.357

The polycombprotein ring1 interacts with the lim domains of kyot2 in yeast and mammalian cells. The interaction between kyot2 and ring1 was detected both in vitro and in vivo

SIGNOR-123150

Q9HAZ1

Q07955

1

phosphorylation

up-regulates activity

0.357

In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors.

SIGNOR-273860

P17252

P49841

1

phosphorylation

down-regulates

0.357

Gsk3 is different from most kinases in that it is constitutively partially active and the most common regulatory mechanism is inhibition by phosphorylation of ser21 in gsk3_ or ser9 in gsk3_. This inhibitory phosphorylation can be mediated by several kinases, such as akt/protein kinase b (pkb), protein kinase c (pkc) and protein kinase a (pka).

SIGNOR-188581

Q86UW7

Q16623

1

binding

up-regulates activity

0.357

CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1

SIGNOR-264337

O60729

Q13309

1

dephosphorylation

down-regulates quantity by destabilization

0.357

The activity of SCF(Skp2) is regulated by the Cyclin-dependent kinase (CDK)2-mediated phosphorylation of Skp2 on Ser64 allows its expression in mid-G1 phase, even in the presence of active APC(Cdh1). Reciprocally, dephosphorylation of Skp2 by the mitotic phosphatase Cdc14B at the M --> G1 transition promotes its degradation by APC(Cdh1).

SIGNOR-248333

Q09472

P52292

1

acetylation

up-regulates

0.357

Ampk triggered the acetylation of importin alpha1 on lys(22), a process dependent on the acetylase activity of p300

SIGNOR-128625

O15530

Q13153

1

phosphorylation

up-regulates activity

0.357

P21-activated kinase (PAK1) is phosphorylated and activated by 3-phosphoinositide-dependent kinase-1 (PDK1). We identify threonine 423, a conserved threonine in the activation loop of kinase subdomain VIII, as the PDK1 phosphorylation site on PAK1.

SIGNOR-250267

P07948

Q9Y6K9

1

phosphorylation

down-regulates activity

0.357

Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.

SIGNOR-276369

Q9P2B4

Q14247

1

binding

up-regulates activity

0.357

CTTNBP2NL interacts with cortactin and targets cortactin to stress fibers.

SIGNOR-261695

Q92949

Q5JVL4

1

transcriptional regulation

up-regulates quantity by expression

0.356

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266934

Q05D32

Q8N165

1

dephosphorylation

up-regulates quantity by stabilization

0.356

We found that peptides corresponding to phosphoserines 194 and 216 of PDIK1L (S385 and S413 of STK35) were efficiently dephosphorylated by SCP4, whereas no activity was detected for the other two phosphopeptides (Figure 6D).

SIGNOR-273773

P01106

P22626

1

transcriptional regulation

up-regulates quantity by expression

0.356

We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2,

SIGNOR-268691

P43405

Q8N6F7

1

phosphorylation

up-regulates activity

0.356

Herein, we demonstrate phosphorylation of HGAL by Syk and Lyn kinases at tyrosines Y80, Y86, Y106Y107, Y128, and Y148. Y148 (in black) was already phosphorylated before the addition of kinases. We demonstrate that Grb2 facilitates HGAL and Syk binding following BCR stimulation but does not affect the HGAL-mediated increase in Syk kinase activity. Previous studies showed that Grb2 inhibits BCR signaling by decreasing the activation of Syk by Lyn.11 Thus, while HGAL and Grb2 oppositely affect Syk kinase activity, this is not due to direct Grb2 effects on HGAL-mediated Syk kinase activation.

SIGNOR-273570

Q9Y2R2

Q96P20

1

dephosphorylation

up-regulates activity

0.356

Further, this explains how loss of PTPN22 and subsequent enhanced NLRP3 phosphorylation mediate a decrease in NLRP3 inflammasome activation.|Upon NLRP3 activation, PTPN22 dephosphorylates NLRP3 and thereby protects it from degradation, allowing robust inflammasome activity (summarized in Fig.S6).

SIGNOR-277056

P62136

Q00987

1

dephosphorylation

up-regulates quantity by stabilization

0.356

Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.

SIGNOR-248566

P31749

Q13188

1

phosphorylation

down-regulates

0.356

We determined that mst2 phosphorylation by akt limits mst2 activity in two ways: first, by blocking its binding to rassf1a and by promoting its association into the raf-1 inhibitory complex, and second, by preventing homodimerization of mst2, which is needed for its activation. we identified t117 and t384 as akt phosphorylation sites in mst2.

SIGNOR-163533

Q15139

O75628

1

phosphorylation

up-regulates activity

0.356

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

SIGNOR-273832

Q13237

Q12778

1

phosphorylation

up-regulates activity

0.356

Biochemical assays using mammalian cGKII and FoxO1 reveal that cGKII enhances the transcriptional activity of FoxO1 through phosphorylation of the FoxO1 S319 site in the same manner as LRRK2.

SIGNOR-279564

Q9UNE7

P17542

1

ubiquitination

down-regulates quantity by destabilization

0.356

Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. CHIP promoted Tal1 degradation with both chaperone binding and ubiquitin ligase activities, which are mediated by its TPR domain and U box, respectively.

SIGNOR-271393

Q9UBN7

Q01130

1

deacetylation

up-regulates

0.356

Our data support a model in which hdac6 has a key role in the maintenance of srsf2 protein level by inhibiting tip60_mediated acetylation and proteasomal degradation.

SIGNOR-170590

Q13616

Q9Y4X5

1

binding

up-regulates activity

0.356

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-268844

P31431

O14640

1

binding

up-regulates

0.356

Like other wnt co-receptors, syndecan 4 directly interacts with dvl during pcp 1.

SIGNOR-199632

P11802

P43694

1

phosphorylation

up-regulates activity

0.356

In addition, we have shown that CDK4 can enhance cardiogenic activity of GATA4 (XREF_FIG).|The physical and functional interactions between GATA4 and Cyclin D2 depend on phosphorylation of Ser 160 of GATA4, which can be mediated in vitro by CDK4.

SIGNOR-279148

O14920

P08151

1

phosphorylation

up-regulates activity

0.356

Active IKKbeta promotes the stability of GLI1 oncogene in diffuse large B-cell lymphoma.|Herein, we demonstrate that IKKbeta phosphorylates GLI1 in DLBCL.

SIGNOR-279194

Q01664

P08047

1

binding

up-regulates activity

0.356

We also observed moderately increased recruitment of CTCF, HDAC1, and SP1 by the full-length AP-4 onto the WT DNA beads.

SIGNOR-226593

P01106

P17480

1

transcriptional regulation

up-regulates quantity by expression

0.356

MAD1 and c-MYC regulate UBF and rDNA transcription during granulocyte differentiation|MAD1 repressed and c-MYC activated rDNA transcription in nuclear run-on assays. Repression of rDNA transcription by MAD1 was associated with its ability to interact directly with the promoter of upstream binding factor (UBF), an rDNA regulatory factor. Conversely, c-MYC activated transcription from the UBF promoter.

SIGNOR-269644

Q00535

Q13794

1

phosphorylation

down-regulates

0.356

We show that noxa is phosphorylated on a serine residue (s(13)) in the presence of glucose. Phosphorylation promotes its cytosolic sequestration and suppresses its apoptotic function. We identify cdk5 as the noxa kinase

SIGNOR-170357

Q9UQ88

O95238

1

phosphorylation

down-regulates quantity by destabilization

0.356

In this study we provide evidence that the cell cycle kinase CDK11p58, a protein involved in G2/M transition and degradation of several transcription factors, directly interacts with and phosphorylates SPDEF on serine residues|Western blot analysis demonstrated that only one of the mutant constructs, consisting of mutations of serine 238, 242 and 243, resulted in increased levels of SPDEF protein expression as compared to wild type SPDEF, leading to subsequent ubiquitination and degradation of SPDEF through the proteasome pathway.|

SIGNOR-273022

Q00535

Q8IV63

1

phosphorylation

up-regulates activity

0.356

Vaccinia-related kinase 3 (VRK3), a member of the VRK family, is widely expressed in human tissues and increases VHR phosphatase activity through a direct binding|Here we report that oxidative stress-induced cyclin-dependent kinase 5 (CDK5) activation stimulates neuroprotective signaling via phosphorylation of vaccinia-related kinase 3 (VRK3) at Ser 108. The binding of vaccinia H1-related (VHR) phosphatase to phosphorylated VRK3 increased its affinity for phospho-ERK and subsequently downregulated ERK activation|

SIGNOR-275544

Q9UNE7

O15519

1

ubiquitination

down-regulates quantity by destabilization

0.356

Taken together, our data suggest that CHIP interacts with c-FLIP L in vivo and promotes the ubiquitination of c-FLIP L.|When we knocked down CHIP, c-FLIP L degradation was inhibited after treatment with 17-AAG, which indicated that CHIP modulated c-FLIP L degradation in the NSCLC cell lines.

SIGNOR-278783

Q08211

P52948

1

binding

up-regulates activity

0.356

Here we report on the identification of the DExH/D-box helicase DHX9 as an intranuclear Nup98 binding partner. Various results, including in vitro assays, show that the FG/GLFG region of Nup98 binds to N- and C-terminal regions of DHX9 in an RNA facilitated manner. Importantly, binding of Nup98 stimulates the ATPase activity of DHX9, and a transcriptional reporter assay suggests Nup98 supports DHX9-stimulated transcription.

SIGNOR-260954

Q00987

O15055

1

polyubiquitination

down-regulates quantity by destabilization

0.356

We identified PER2 as a previously uncharacterized substrate for the ubiquitin ligase mouse double minute 2 homolog (MDM2) and found that MDM2 targeted PER2 for degradation in a manner independent of PER2 phosphorylation.

SIGNOR-277421

P23443

Q92519

1

phosphorylation

down-regulates quantity by destabilization

0.356

Furthermore, Smurf1-mediated ubiquitination required phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino acids 69-85) that is also essential for correct TRIB2 subcellular localization. Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2.

SIGNOR-275433

P21918

P09471

1

binding

up-regulates activity

0.356

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-257244

P34947

Q9UQL6

1

phosphorylation

down-regulates activity

0.356

GRK5 phosphorylates and promotes the nuclear export of the histone deacetylase, HDAC5.

SIGNOR-279045

O75592

P49815

1

ubiquitination

down-regulates quantity by destabilization

0.356

We show that Pam associates with E2 ubiquitin conjugating enzymes, and tuberin can be ubiquitinated by Pam through its RING finger domain.

SIGNOR-278704

P06493

O95251

1

phosphorylation

up-regulates

0.355

Here, we show that the interaction between plk1 and hbo1 is mitosis-specific and that plk1 phosphorylates hbo1 on ser-57 in vitro and in vivo. During mitosis, cdk1 phosphorylates hbo1 on thr-85/88, creating a docking site for plk1 to be recruited. Significantly, the overexpression of hbo1 mutated at the plk1 phosphorylation site (s57a) leads to cell-cycle arrest in the g1/s phase, inhibition of chromatin loading of the minichromosome maintenance (mcm) complex, and a reduced dna replication rate.

SIGNOR-160747

Q13490

P57078

1

polyubiquitination

up-regulates activity

0.355

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.

SIGNOR-272708

P06493

P68400

2

phosphorylation

up-regulates

0.355

Four residues within this domain, thr-344, thr-360, ser-362, and ser-370, conform to the minimal consensus sequence for p34cdc2 phosphorylationthe high stoichiometry of phosphorylation suggests that phosphorylation could regulate functional properties of ckii and that it could in some way participate in the burst of phosphorylation that accompanies the activation of p34graphic at the ggraphic-m transition

SIGNOR-29525

P68400

P06493

2

phosphorylation

up-regulates

0.355

Additionally, transfection of cdc2 with a mutation at ser(39) to ala, which is the ck2 phosphorylation site, partially inhibits cell cycle progression in g(1) to g(2) phase following 6-tg treatment.

SIGNOR-134846

Q13489

P57078

1

polyubiquitination

up-regulates activity

0.355

CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.Lysine residues K51 and K145 of RIP4 are critical for cIAP1-mediated ubiquitination and NF-kB activation.

SIGNOR-272709

P31749

P29317

1

phosphorylation

up-regulates activity

0.355

As non-canonical EphA2 activation requires phosphorylation of EphA2 at serine 897 by pAkt (Fig.\u00a02b), we sought to determine the effect of PTEN-mediated Akt regulation on invasion.

SIGNOR-279787

Q6ZNA4

P29590

1

polyubiquitination

down-regulates quantity by destabilization

0.355

Upon TGF-β induction, interaction of Arkadia with phosphorylated Smad2 triggers degradation of SnoN, whereas upon arsenic treatment, interaction of Arkadia with poly-SUMO in PML nuclear bodies induces degradation of polysumoylated PML together with RNF4.

SIGNOR-272883

P23469

Q14721

1

dephosphorylation

down-regulates activity

0.355

Hypomyelination and increased activity of voltage-gated K(+) channels in mice lacking protein tyrosine phosphatase epsilon

SIGNOR-248450

P06493

O94761

1

phosphorylation

up-regulates activity

0.355

During S/G2 phases, CDK1 and CDK2 (CDK1/2) phosphorylate RECQL4 on serines 89 and 251, enhancing MRE11/RECQL4 interaction and RECQL4 recruitment to DSBs.

SIGNOR-277375

P12931

P51812

1

phosphorylation

up-regulates

0.355

Together, our findings suggest that src-dependent phosphorylation at tyr-529 facilitates inactive erk binding to rsk2, which might be a general requirement for rsk2 activation by egf through the mek/erk pathway.

SIGNOR-160052

Q15139

Q9BST9

1

phosphorylation

up-regulates activity

0.355

Here, we show that rhotekin, an effector of RhoA GTPase, is a novel substrate of PKD. We identified Ser-435 in rhotekin as the potential site targeted by PKD in vivo. Expression of a phosphomimetic S435E rhotekin mutant resulted in an increase of endogenous active RhoA GTPase levels. Phosphorylation of rhotekin by PKD2 modulates the anchoring of the RhoA in the plasma membrane.

SIGNOR-275511

P08631

Q13444

1

phosphorylation

up-regulates

0.355

Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.

SIGNOR-112919

P04150

P06239

1

binding

up-regulates

0.355

The present study shows that the GC receptor is part of a TCR-linked multiprotein complex containing heat-shock protein (HSP)90, LCK and FYN, which is essential for TCR-dependent LCK/FYN activation.

SIGNOR-251685

P24723

Q15139

1

phosphorylation

up-regulates

0.355

These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.

SIGNOR-66734

Q9H1C0

Q03113

1

binding

up-regulates activity

0.355

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-257205

P23443

P78362

1

phosphorylation

up-regulates activity

0.355

Altogether, these results identify S6K1-phosphorylated SRPK2 as an essential mediator of IGF1-stimulated SG formation in hPDAC cells.|The nodes of the core SG network are known to contribute to SG formation to varying degrees and it is possible that S6K1-stimulated SRPK2 may impact their contribution; this is consistent with the predicted model whereby SG assembly is subject to regulation by positive and negative cooperativity of extrinsic factors with the core network interactions (14).

SIGNOR-280121

Q15208

Q9BX46

1

phosphorylation

up-regulates activity

0.355

Phosphorylation of Rbm24 by Stk38 is crucial for the maintenance of cardiac sarcomeric gene expression in cardiac cells.|These results indicated that Stk38 increases Rbm24 protein stability probably by interfering with the ubiquitin-proteasome protein degradation pathway.

SIGNOR-278291

Q13315

Q9NY61

1

phosphorylation

up-regulates quantity by stabilization

0.355

The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. |DNA damage stabilizes Che-1 protein|In addition, substitution of Che-1 Ser187 with an alanine (Che-1S187A) prevented Che-1 phosphorylation by ATM (Figure 2F), supporting this residue as an ATM-target site.

SIGNOR-264415

P45984

P12931

1

phosphorylation

up-regulates activity

0.355

Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.

SIGNOR-279221

Q86X55

P40925

1

acetylation

down-regulates activity

0.355

Arginine Methylation of MDH1 by CARM1 Inhibits Glutamine Metabolism and Suppresses Pancreatic Cancer|Arginine methylation at R248 negatively regulates MDH1 activity|PRMT4/CARM1 methylates MDH1 at R248 and inhibits its dimerization

SIGNOR-267639

Q04759

P22681

1

phosphorylation

up-regulates activity

0.355

PKC-θ-mediated phosphorylation of serine and tyrosine residues of c-Cbl prevents its inhibitory effect. Phosphorylation of c-Cbl by PKC-θ inhibits the recruitment of Sh2-containing proteins and subsequent association of cbl E3 ubiquitin ligase with its target proteins

SIGNOR-274144

Q96BR1

Q13045

1

phosphorylation

up-regulates

0.355

Here we show that flii is an in vivo substrate of cisk that functions downstream of pi 3-kinase. Cisk can associate with flii and phosphorylate flii at residues ser(436) and thr(818).We demonstrate here that cisk can enhance er transcription, which is dependent on its kinase activity, and mutation of cisk phosphorylation sites on flii attenuates its activity as an er co-activator.

SIGNOR-184688

Q05086

P20618

1

ubiquitination

down-regulates quantity by destabilization

0.355

Our experiments collectively suggest that UBE3A stimulates Wnt pathway activation by interacting with, ubiquitinating, and reducing the levels of multiple (PSMB1, PSMC2, PSMD2, and PSMD7) proteasome subunits.

SIGNOR-265131

P50570

O00159

1

binding

up-regulates

0.355

Dynamin bind directly to the sh3 domain of myo1e / an intriguing possibility is that binding of dynamin and synaptojanin to myo1e tail may activate motor activity since it has been demonstrated that myo1e atpase activity is autoinhibited by its sh3 domain

SIGNOR-152910

Q05655

Q15080

1

phosphorylation

up-regulates activity

0.355

P40(phox) is phosphorylated on threonine 154 and serine 315 during activation of the phagocyte NADPH oxidase. Implication of a protein kinase c-type kinase in the phosphorylation process.

SIGNOR-249012

P06493

O15287

1

phosphorylation

up-regulates

0.355

S387a mutant abolished fancg fusion protein phosphorylation by cdc2.

SIGNOR-129061

P31749

Q8IYJ3

1

phosphorylation

down-regulates quantity

0.355

By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241. Phosphorylation did not alter the ability of JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo phosphorylation, JFC1 dissociates from the membrane, promoting JFC1 redistribution to the cytosol.

SIGNOR-273540

Q9NWF9

Q8IUC6

1

ubiquitination

down-regulates quantity by destabilization

0.355

Triad3A promotes proteolytic degradation of adapter proteins. A, Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.

SIGNOR-271609

P49841

Q08050

1

phosphorylation

down-regulates quantity by destabilization

0.355

GSK3 phosphorylates FoxM1 on serine 474 which induces FoxM1 ubiquitination mediated by FBXW7.

SIGNOR-277208

Q7Z6J0

Q02779

1

binding

up-regulates

0.355

Taken together, these findings support a model in which apoptotic stimuli or posh overexpression induce direct association between posh and inactive mlks.

SIGNOR-97003

P06493

P23769

1

phosphorylation

down-regulates quantity by destabilization

0.355

GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1).

SIGNOR-276884

P00519

O75496

1

phosphorylation

up-regulates activity

0.355

Taken together, suggests that c-Abl binds and phosphorylates geminin on Y150 in G2/M/early G1 phases.

SIGNOR-278505

Q9Y463

P46527

1

phosphorylation

up-regulates

0.355

Mirk phosphorylates p27 at ser-10, thus stabilizing p27 and blocking its nuclear export and degradation

SIGNOR-235805

Q02078

P12882

1

transcriptional regulation

up-regulates quantity by expression

0.355

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-238748

P28482

O94811

1

phosphorylation

down-regulates activity

0.354

Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.

SIGNOR-262928

P18031

P78337

1

dephosphorylation

down-regulates quantity by destabilization

0.354

PTP1B dephosphorylates PITX-1 at Y160, 175 and Y179.|Through directly dephosphorylating PITX-1 at Y160, Y175 and Y179, PTP1B promoted proteasomal degradation of PITX-1, thus leaded in downregulating p120RasGAP and CRC cell survival.

SIGNOR-276973

P48729

P07910

1

phosphorylation

down-regulates

0.354

A kinase activity was identified in mouse liver that phosphorylates the acd of hnrnp-c at ser(240) and at two sites at ser(225)-ser(228). The kinase was purified and identified by tandem mass spectrometry as protein kinase ck1alpha (formerly casein kinase 1alpha).hnrnp-c1 that was also modified at the ck1alpha phosphorylation sites exhibited a 14-500-fold decrease in binding affinity, demonstrating that ck1alpha-mediated phosphorylation modulates the mrna binding ability of hnrnp-c.

SIGNOR-133528

P18031

P25963

1

dephosphorylation

down-regulates

0.354

Ptp1b is able to dephosphorylate phosphorylated-tyr-42 on ikappabalpha

SIGNOR-45004

P28482

P50616

1

phosphorylation

down-regulates

0.354

Tob is rapidly phosphorylated at ser 152, ser 154, and ser 164 by erk1 and erk2 upon growth-factor stimulation.

SIGNOR-88720

P53350

Q8IWB6

1

phosphorylation

down-regulates quantity by destabilization

0.354

We show that phosphorylation of Tex14 by Plk1 during metaphase is required for proteosome dependent degradation of Tex14 and transition from metaphase to anaphase. Phosphorylation of Tex14 Ser431 by Plk1 promotes Tex14 depletion.

SIGNOR-273529

Q13976

Q9Y613

1

phosphorylation

up-regulates

0.354

Pkgi also directly phosphorylates fhod1, and studies with wild-type and mutant fhod1-derived peptides identify ser-1131 in the fhod1 c terminus as the unique pkgi phosphorylation site in fhod1. phosphorylation of three conserved residues within the dad domain activates fhod1 while binding to rac regulates fhod1 subcellular localization

SIGNOR-123646

P53350

P18031

1

phosphorylation

up-regulates activity

0.354

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

SIGNOR-272990

P54821

Q9ULX9

1

binding

down-regulates activity

0.354

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-221890

P09874

Q9UGL1

1

relocalization

up-regulates activity

0.354

The mechanism of KDM5B recruitment is quite specific and requires the presence of nucleosomes containing histone variant MacroH2A1.1 and PARylation by PARP1.

SIGNOR-271574

Q9UIK4

Q8N122

1

phosphorylation

down-regulates activity

0.354

DAPK2 phosphorylates raptor in vitro on Ser721.

SIGNOR-278243

Q9Y243

O15119

1

phosphorylation

up-regulates activity

0.354

We have identified TBX3 as a key substrate of AKT3 in melanomagenesis. we have identified the AKT3 target site at serine residue 720 in the TBX3 protein and show that this site is phosphorylated in vivo. the phosphorylation at S720 promotes TBX3 protein stability, nuclear localization, transcriptional repression of E-cadherin, and its role in cell migration and invasion.

SIGNOR-223534

P28482

Q15648

1

phosphorylation

up-regulates

0.354

We demonstrate that erk phosphorylates trap220/med1 in vivo at two specific sites: threonine 1032 and threonine 1457. importantly, we found that erk phosphorylation significantly increases the stability and half-life of trap220/med1 in vivo and correlates with increased thyroid hormone receptor-dependent transcription.

SIGNOR-142462

Q96BR1

P49840

1

phosphorylation

down-regulates activity

0.354

Phosphorylation of GSK3 by PKB or SGK1 inhibits GSK3 activity|estern blotting using an antibody specific for the PKB/SGK1 consensus phosphorylation site in GSK3a/beta (serine 21 and 9 respectively) revealed an increase in GSK3a/beta phosphorylation in human embryonic kidney 293 (HEK293) cells overexpressing wild type SGK1, constitutively active SGK1, but not catalytically inactive SGK1.|The effect of SGK1 was mimicked by PKB and SGK3.

SIGNOR-249165

P31749

P07550

1

phosphorylation

down-regulates

0.354

Akt mediates sequestration of the beta(2)-adrenergic receptor in response to insulin. Phosphorylation studies of the c-terminal cytoplasmic domain of the beta(2)-adrenergic receptor by akt in vitro identified ser(345) and ser(346) within a consensus motif for akt phosphorylation.

SIGNOR-252470

P06239

P24666

1

phosphorylation

up-regulates activity

0.354

In co-transfected COS cells, Lck and Fyn caused phosphorylation of LMPTP. Most of the phosphate was located at Tyr-131, and some was also located at Tyr-132. Site-directed mutagenesis showed that Tyr-131 is important for the catalytic activity of LMPTP, and that thiophosphorylation of Tyr-131, and to a lesser degree Tyr-132, is responsible for the activation.

SIGNOR-251367

Q15262

Q9ULT6

1

dephosphorylation

up-regulates activity

0.354

We show that PTPRK acts via the transmembrane E3 ubiquitin ligase ZNRF3, a negative regulator of Wnt signaling promoting Wnt receptor degradation, which is also expressed in the organizer.

SIGNOR-260110

P27361

P35228

1

phosphorylation

up-regulates

0.354

Erk phosphorylated inos on ser745. Mutation of ser745 to ala did not affect basal inos activity but eliminated inos phosphorylation and activation in response to b1r agonist.

SIGNOR-157711

Q13315

Q9UGP5

1

phosphorylation

up-regulates activity

0.354

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

SIGNOR-273836

A1L390

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.354

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

SIGNOR-260585

P68400

Q15185

1

phosphorylation

up-regulates

0.354

Several lines of evidence suggest that a cpges-activating protein kinase is ck-ii (casein kinase ii). Recombinant cpges was phosphorylated directly by and associated with ck-ii in vitro, resulting in marked reduction of the k m for the substrate pgh2.

SIGNOR-123594