GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q96EP1	Q96EB6	1	ubiquitination	down-regulates quantity	0.372	CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.\|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.	SIGNOR-278691
P61204	Q9Y6D6	0	guanine nucleotide exchange factor	up-regulates activity	0.366	Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.	SIGNOR-272148
P53611	P20336	1	lipidation	up-regulates activity	0.656	Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional	SIGNOR-265575
Q96GD4	Q08J23	1	phosphorylation	down-regulates	0.72	Aurora-b phosphorylated nsun2 at ser139. Aurora-b-phosphorylation and the phosphorylation-mimic mutation (s139e) suppressed methyltransferase activities of nsun2.	SIGNOR-152001
Q8TDY2	O75385	0	phosphorylation	up-regulates	0.913	Ulk1 and ulk2 are the kinase phosphorylating their binding proteins atg13 and fip200. Atg13 directly binds fip200 and mediates the interaction between fip200 and ulks.	SIGNOR-186992
O75385	Q96KB5	0	phosphorylation	down-regulates activity	0.2	We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1.	SIGNOR-277473
P17612	P52565	1	phosphorylation	down-regulates	0.387	The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.	SIGNOR-180576
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
O15169	O95271	0	ubiquitination	down-regulates quantity by destabilization	0.774	Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway.	SIGNOR-187972
Q15853	P49841	0	phosphorylation	up-regulates activity	0.283	Although no study has yet correlated the activity of GSK3beta with the activity of USF2 in a certain tumor setting, the findings of the present study would favor the tumor promoting aspects of GSK3beta and USF2 since GSK3beta activated USF2 enhanced cell migration which may be important in terms of tumor cell metastasis.\|Together, these data show that there are two residues within USF2, namely S155 and T230, which can be phosphorylated by GSK3beta.	SIGNOR-278158
P51955	Q07955	1	phosphorylation	down-regulates activity	0.385	First, NEK2 interacts with and phosphorylates SRSF1.	SIGNOR-279344
P46531	P24863	0	phosphorylation	down-regulates	0.48	Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.	SIGNOR-130592
Q5FWF5	P06493	0	phosphorylation	down-regulates	0.474	We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases , cdc7-dbf4 and the gsk-3 homolog mck1.	SIGNOR-200400
Q05655	P09758	1	phosphorylation	down-regulates activity	0.2	Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.	SIGNOR-273820
Q13233	Q15796	1	phosphorylation	up-regulates activity	0.474	As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.\|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .	SIGNOR-279064
Q99961	Q5S007	0	phosphorylation	down-regulates	0.467	We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association.	SIGNOR-192068
Q13285	P50613	0	phosphorylation	up-regulates	0.366	In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1	SIGNOR-157952
Q8TDZ2	P00519	0	phosphorylation	up-regulates activity	0.312	Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.\|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.	SIGNOR-279674
O00506	O43561	1	phosphorylation	up-regulates activity	0.2	In sum, these data reveal that STK25 activates LATS kinases through a mechanism that is distinct from what has been characterized for the MAP4K/MST kinases (Fig.\u00a0 xref ).\|Mechanistically, we demonstrate that STK25 promotes LATS phosphorylation at the activation loop in the absence of hydrophobic motif phosphorylation, which distinguishes it from all of the other known LATS-activating kinases discovered to date.	SIGNOR-279294
O95835	Q14344	0	phosphorylation	down-regulates activity	0.2	These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes	SIGNOR-278051
Q9UI32	P04637	0	transcriptional regulation	up-regulates quantity by expression	0.631	Glutaminase 2 (GLS2) can be directly transactivated by p53 and can therefore mediate p53-dependent regulation of cellular energy metabolism. G	SIGNOR-268041
P03372	P27361	0	phosphorylation	up-regulates	0.704	In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo.Phosphorylation at serines 104 and 106 by erk1/2 mapk is important for estrogen receptor-alpha activity	SIGNOR-156864
Q03112	O15123	1	transcriptional regulation	up-regulates quantity by expression	0.2	We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2	SIGNOR-266060
P52945	P78426	1	transcriptional regulation	up-regulates quantity by expression	0.503	In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.	SIGNOR-255542
P42574	P98170	0	ubiquitination	down-regulates quantity by destabilization	0.939	Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.	SIGNOR-109243
O00418	P23443	0	phosphorylation	down-regulates activity	0.736	We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity	SIGNOR-109712
P00519	P12532	1	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2+ breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation.	SIGNOR-277406
P06241	P06239	1	phosphorylation	down-regulates activity	0.411	In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.\|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.	SIGNOR-279986
O14829	O14737	1	dephosphorylation	down-regulates quantity by destabilization	0.349	Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.\|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.	SIGNOR-277008
P63000	Q9P107	0	gtpase-activating protein	down-regulates activity	0.445	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-260506
P20336	Q15042	0	gtpase-activating protein	down-regulates activity	0.439	Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).	SIGNOR-265580
Q5U5R9	O75925	1	polyubiquitination	down-regulates quantity by destabilization	0.389	We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model.	SIGNOR-272421
Q9ULT6	O75581	1	ubiquitination	down-regulates quantity	0.656	Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.	SIGNOR-260112
P00352	O14965	0	phosphorylation	up-regulates activity	0.372	AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.	SIGNOR-276748
P20393	Q99743	1	transcriptional regulation	down-regulates quantity by repression	0.631	In this study, we found that NPAS2, like BMAL1, is a direct target gene of RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding.	SIGNOR-267981
P30304	P20248	1	dephosphorylation	up-regulates activity	0.692	Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .	SIGNOR-277136
P06730	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.332	This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis.\|We next sought to investigate whether eIF4E ubiquitination is enhanced by the collaborative activity of cIAP1 and CHIP, which we define as both the E3 ligase activity of cIAP1 alone and the E3 ligase activity of cIAP1 and CHIP together.	SIGNOR-278669
P05198	Q9NR50	0	guanine nucleotide exchange factor	up-regulates activity	0.833	EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity.	SIGNOR-269126
P12931	Q96KB5	1	phosphorylation	up-regulates quantity by stabilization	0.395	Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon	SIGNOR-277217
Q9H3R0	P84243	1	demethylation	down-regulates activity	0.2	As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation	SIGNOR-263869
P13807	Q9Y463	0	phosphorylation	down-regulates activity	0.258	DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.	SIGNOR-260633
O43257	P15173	1	transcriptional regulation	up-regulates quantity by expression	0.259	We show that the srcap subunit named znhit1 or p18hamlet, which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. We also show that p18hamlet is required for h2a.z accumulation into this genomic region and for subsequent muscle gene transcriptional activation.	SIGNOR-165613
P09848	Q99626	0	transcriptional regulation	up-regulates quantity by expression	0.362	By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1.	SIGNOR-253964
Q8IXI1	O60260	0	polyubiquitination	down-regulates quantity by destabilization	0.2	PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.	SIGNOR-272726
Q13936	P17612	0	phosphorylation	up-regulates activity	0.498	These findings reveal an essential role for _1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes	SIGNOR-251709
P31749	P45983	0	phosphorylation	up-regulates activity	0.427	We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase.	SIGNOR-252426
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
Q92934	Q86V86	0	phosphorylation	down-regulates activity	0.346	Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.	SIGNOR-250399
P14923	P16591	0	phosphorylation	up-regulates activity	0.526	The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin)	SIGNOR-251134
O14713	O96013	0	phosphorylation	down-regulates activity	0.2	We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.\|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.	SIGNOR-280056
P25490	P07948	0	phosphorylation	down-regulates activity	0.2	In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).	SIGNOR-276930
P60953	Q9H4E7	0	guanine nucleotide exchange factor	up-regulates activity	0.392	Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.	SIGNOR-253369
P49841	Q15418	0	phosphorylation	down-regulates	0.359	S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.	SIGNOR-110917
Q92974	P28482	0	phosphorylation	up-regulates	0.358	Importantly tnf-alpha enhanced the erk pathway-dependent phosphorylation of thr-678 of gef-h1 that was key for activation.	SIGNOR-184469
Q99704	O14920	0	phosphorylation	up-regulates	0.253	Ikkbeta phosphorylates dok1 s(439)s(443) and s(446)s(450) after tnf-alpha, il-1, or gamma-radiation. mutant dok1 a(439), a(443), a(446), and a(450) differed from wild-type dok1 in not inhibiting platelet-derived growth factor-induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth. Mutant dok1 a(439), a(443), a(446), and a(450) also did not promote cell motility whereas wild-type dok1 promoted cell motility.	SIGNOR-131447
Q13263	P60510	0	dephosphorylation	down-regulates activity	0.358	PP4 dephosphorylated pKAP1 in vitro.	SIGNOR-277163
Q07666	P06241	0	phosphorylation	up-regulates activity	0.544	The tyrosine kinase Fyn modulates Sam68 mediated alternative splicing of Bcl-x mRNA.\|Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection.	SIGNOR-279462
P60953	Q07960	0	gtpase-activating protein	down-regulates activity	0.905	We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)\|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs\| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).	SIGNOR-260459
Q9NWF9	Q13546	1	ubiquitination	down-regulates quantity by destabilization	0.503	Triad3A promotes proteolytic degradation of adapter proteins. Triad3A promotes down-regulation of TIRAP, TRIF, and RIP1 proteins.	SIGNOR-271608
P49840	Q04206	1	phosphorylation	up-regulates activity	0.2	Redundant functions of GSK-3_ and GSK-3_ through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation	SIGNOR-255827
P49841	Q2M1Z3	1	phosphorylation	up-regulates activity	0.302	We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.	SIGNOR-262879
P06213	Q12913	0	dephosphorylation	down-regulates	0.304	Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.	SIGNOR-21295
Q92953	Q9P0L0	1	relocalization	up-regulates quantity	0.2	Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.\|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.	SIGNOR-262124
Q12959	P11171	0	relocalization	up-regulates activity	0.472	Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.	SIGNOR-266011
Q92630	O95863	1	phosphorylation	down-regulates activity	0.346	DYRK2 mediated Snail degradation protects against tumor cell metastasis.\|DYRK2 phosphorylation of Snail at Ser104 triggers sequential phosphorylation by GSK3.	SIGNOR-279328
Q96Q27	P21333	1	polyubiquitination	down-regulates quantity by destabilization	0.442	ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation.	SIGNOR-271740
P00519	Q92993	1	phosphorylation	down-regulates activity	0.647	We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65.	SIGNOR-276598
Q13153	P15336	1	phosphorylation	down-regulates activity	0.2	Overall, our results unequivocally confirmed that Pak1 physically interacts with ATF2 and phosphorylates ATF2 on the Ser62 residue, and this process secludes ATF2 in the cytoplasm.	SIGNOR-279377
P49841	Q9UQB3	1	phosphorylation	down-regulates quantity	0.347	Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.\|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin.	SIGNOR-279719
Q86VW2	P61586	1	guanine nucleotide exchange factor	up-regulates activity	0.835	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-260544
Q01344	P07948	0	phosphorylation	up-regulates activity	0.475	Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL.\|We further delineated that Lyn can induce IL-5RA tyrosine phosphorylation and physically associate with IL-5RA in F/P expressing cells.	SIGNOR-279059
O95835	P11908	1	phosphorylation	down-regulates quantity by destabilization	0.2	Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.	SIGNOR-276506
Q9UHD2	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.456	Nuclear factor-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkapapB. TBK-1 and IKK-i phosphorylate Ser36 of IkappaBalpha.	SIGNOR-246643
Q9H2X6	P16220	1	phosphorylation	up-regulates	0.389	Ere we found that homeodomain-interacting protein kinase 2 (hipk2), a dna-damage responsive nuclear kinase, is a new creb kinase for phosphorylation at ser-271 but not ser-133, and activates creb transactivation function	SIGNOR-166338
Q96A54	P25098	0	phosphorylation	down-regulates activity	0.2	AdipoR1 is Directly Phosphorylated by GRK2.\|In summary, our study demonstrates for the first time that cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2 mediated AdipoR1 phosphorylative desensitization during a critical period of post-MI HF development.	SIGNOR-279463
Q13557	Q08289	1	phosphorylation	up-regulates	0.412	We recently identified ca(v)1.2 beta(2a) residues critical for camkii phosphorylation (thr 498) beta(2a) thr 498 and leu 493 are required for ca(v)1.2 activation by camkii in native cells.	SIGNOR-164067
P49336	P46937	1	phosphorylation	up-regulates activity	0.321	CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.	SIGNOR-277651
Q9P286	Q04206	1	phosphorylation	up-regulates activity	0.2	PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo\|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1	SIGNOR-275657
Q9HA77	P18848	0	transcriptional regulation	up-regulates quantity by expression	0.257	QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.	SIGNOR-269417
P10586	P06239	1	dephosphorylation	up-regulates	0.364	We confirmed that lar dephosphorylated the phosphorylated tyrosine residues of lck..Activation Of lck and fyn involves tyrosine dephosphorylation of the cooh-terminal regulatory domain of kinases, followed by autophosphorylation of the kinase domain.	SIGNOR-96771
Q4VCS5	O95835	0	phosphorylation	up-regulates quantity by stabilization	0.523	Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130	SIGNOR-275843
P27708	P17612	0	phosphorylation	down-regulates	0.307	Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade.	SIGNOR-151816
Q9H6Z4	Q15418	0	phosphorylation	up-regulates quantity	0.319	RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran	SIGNOR-276149
P08047	Q8N695	1	transcriptional regulation	up-regulates quantity by expression	0.2	Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription.	SIGNOR-254059
P49715	P28845	1	transcriptional regulation	up-regulates quantity by expression	0.274	Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region.	SIGNOR-268971
P19338	P68871	1	post transcriptional regulation	up-regulates quantity by expression	0.2	Nucleolin binds human β-globin mRNA. A Nucleolin-Binding 3′ Untranslated Region Element Stabilizes β-Globin mRNA In Vivo	SIGNOR-251844
P01178-PRO_0000020495	Q92824	0	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270334
Q15831	O14744	1	phosphorylation	up-regulates activity	0.2	We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.	SIGNOR-277412
Q06187	P00519	0	phosphorylation	down-regulates activity	0.336	In this report we describe for the first time that ABL1 and Btk physically interact and that ABL1 can phosphorylate tyrosine 223 in the SH3 domain of Btk. \| This is presumably due to the negative regulatory effectof Btk SH3 domain phosphorylation caused by ABL1,which would result in a decreased catalytic activity ofBtk resulting in impaired autophosphorylation.	SIGNOR-260801
P17252	Q9BR76	1	phosphorylation	down-regulates	0.324	We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.	SIGNOR-138733
P04637	Q9UHC7	0	polyubiquitination	down-regulates quantity by destabilization	0.431	Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. K291 and K292 of p53 are required for MKRN1-mediated degradation and ubiquitination of p53	SIGNOR-271846
Q92824	P01178-PRO_0000020496	1	cleavage	up-regulates quantity	0.2	Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.	SIGNOR-270336
P12830	Q9UHD2	0	phosphorylation	down-regulates activity	0.272	Inhibition of TBK1 increases association of Cdh1 with APC1.\|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).	SIGNOR-278996
Q14247	P18031	0	dephosphorylation	up-regulates activity	0.516	We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.	SIGNOR-277027
P49841	O60346	1	phosphorylation	down-regulates	0.353	In addition, we show that the beta-trcp-mediated degradation requires phosphorylation of phlpp1 by casein kinase i and glycogen synthase kinase 3beta (gsk-3beta), and activation of the phosphatidylinositol 3-kinase/akt pathway suppresses the degradation of phlpp1 by inhibiting the gsk-3beta activity.	SIGNOR-188330
P08236	Q9NR19	0	transcriptional regulation	up-regulates quantity by expression	0.262	Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy\|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1\|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants	SIGNOR-276554
P28482	P04637	1	phosphorylation	up-regulates activity	0.778	In summary, our results suggest that phosphorylation of p53Thr55 by ERK2 is important for doxorubicin-induced p53 activation and cell death.	SIGNOR-279068
Q6ZVD8	P17252	1	dephosphorylation	down-regulates quantity	0.253	In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha	SIGNOR-237051
P18031	P12931	1	dephosphorylation	up-regulates activity	0.781	Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-419 and of Tyr-530	SIGNOR-245299
P07948	P25490	1	phosphorylation	down-regulates activity	0.2	In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).	SIGNOR-276930

Q96EP1

Q96EB6

1

ubiquitination

down-regulates quantity

0.372

CHFR binds to and ubiquitylates SIRT1, leading to its proteasomal degradation.|CHFR ubiquitylates and promotes the proteasomal degradation of SIRT1.

SIGNOR-278691

P61204

Q9Y6D6

0

guanine nucleotide exchange factor

up-regulates activity

0.366

Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximately 200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3.

SIGNOR-272148

P53611

P20336

1

lipidation

up-regulates activity

0.656

Prenylation (or geranylgeranylation) of Rab GTPases is catalysed by RGGT (Rab geranylgeranyl transferase) and requires REP (Rab escort protein). In the classical pathway, REP associates first with unprenylated Rab, which is then prenylated by RGGT. In the alternative pathway, REP associates first with RGGT; this complex then binds and prenylates Rab proteins. Rab GTPases need to be geranylgeranylated on either one or two cysteine residues in their Ctermini in order to localize to the correct intracellular membrane and be functional

SIGNOR-265575

Q96GD4

Q08J23

1

phosphorylation

down-regulates

0.72

Aurora-b phosphorylated nsun2 at ser139. Aurora-b-phosphorylation and the phosphorylation-mimic mutation (s139e) suppressed methyltransferase activities of nsun2.

SIGNOR-152001

Q8TDY2

O75385

0

phosphorylation

up-regulates

0.913

Ulk1 and ulk2 are the kinase phosphorylating their binding proteins atg13 and fip200. Atg13 directly binds fip200 and mediates the interaction between fip200 and ulks.

SIGNOR-186992

O75385

Q96KB5

0

phosphorylation

down-regulates activity

0.2

We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1.

SIGNOR-277473

P17612

P52565

1

phosphorylation

down-regulates

0.387

The results indicate that phosphorylation of gdi_ at ser174 by pka suppresses rhoa activity, providing a potential protective signaling mechanism for inflammatory injury.

SIGNOR-180576

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

O15169

O95271

0

ubiquitination

down-regulates quantity by destabilization

0.774

Both tankyrase isoforms interact with a highly conserved domain of axin and stimulate its degradation through the ubiquitin-proteasome pathway.

SIGNOR-187972

Q15853

P49841

0

phosphorylation

up-regulates activity

0.283

Although no study has yet correlated the activity of GSK3beta with the activity of USF2 in a certain tumor setting, the findings of the present study would favor the tumor promoting aspects of GSK3beta and USF2 since GSK3beta activated USF2 enhanced cell migration which may be important in terms of tumor cell metastasis.|Together, these data show that there are two residues within USF2, namely S155 and T230, which can be phosphorylated by GSK3beta.

SIGNOR-278158

P51955

Q07955

1

phosphorylation

down-regulates activity

0.385

First, NEK2 interacts with and phosphorylates SRSF1.

SIGNOR-279344

P46531

P24863

0

phosphorylation

down-regulates

0.48

Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.

SIGNOR-130592

Q5FWF5

P06493

0

phosphorylation

down-regulates

0.474

We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases , cdc7-dbf4 and the gsk-3 homolog mck1.

SIGNOR-200400

Q05655

P09758

1

phosphorylation

down-regulates activity

0.2

Analyses using HCT116 cells expressing WT Trop-2 (HCT116/WT) or Trop-2 alanine-substituted at Ser-303 (HCT116/S303A) or Ser-322 (HCT116/S322A) revealed that Trop-2 is phosphorylated at Ser-322. sing protein kinase C (PKC) inhibitors and PKC-specific siRNAs, we found that PKCα and PKCδ are responsible for Trop-2 phosphorylation.

SIGNOR-273820

Q13233

Q15796

1

phosphorylation

up-regulates activity

0.474

As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .

SIGNOR-279064

Q99961

Q5S007

0

phosphorylation

down-regulates

0.467

We show that lrrk2 affects synaptic endocytosis by phosphorylating endoa at s75, a residue in the bar domain / our work uncovers a regulatory mechanism that indicates that reduced lrrk2 kinase activity facilitates endoa membrane association, while increased kinase activity inhibits membrane association.

SIGNOR-192068

Q13285

P50613

0

phosphorylation

up-regulates

0.366

In conclusion, our results indicate that cdk7, as part of the cak complex and tfiih, phosphorylates sf1 at s203 followed by increased transcriptional activity of sf1

SIGNOR-157952

Q8TDZ2

P00519

0

phosphorylation

up-regulates activity

0.312

Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly.|We now find that the Abl non receptor protein tyrosine kinase and oncoprotein signaling pathway activates Mical to direct multiple cellular effects - including extending and shaping cellular processes, guiding axons, and orchestrating cancer cell invasion, colony formation, and survival.

SIGNOR-279674

O00506

O43561

1

phosphorylation

up-regulates activity

0.2

In sum, these data reveal that STK25 activates LATS kinases through a mechanism that is distinct from what has been characterized for the MAP4K/MST kinases (Fig.\u00a0 xref ).|Mechanistically, we demonstrate that STK25 promotes LATS phosphorylation at the activation loop in the absence of hydrophobic motif phosphorylation, which distinguishes it from all of the other known LATS-activating kinases discovered to date.

SIGNOR-279294

O95835

Q14344

0

phosphorylation

down-regulates activity

0.2

These findings suggest that Galpha13 induced phosphorilation of LATS1 at S909 recruits ITCH to trigger LATS1 degradation, leading to EMT-related phenotypes

SIGNOR-278051

Q9UI32

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.631

Glutaminase 2 (GLS2) can be directly transactivated by p53 and can therefore mediate p53-dependent regulation of cellular energy metabolism. G

SIGNOR-268041

P03372

P27361

0

phosphorylation

up-regulates

0.704

In several estrogen response element-containing genes, the s118a mutation strongly reduced induction by e(2), and u0126 did not further reduce expression. Here, we show that serines 104 (s104) and 106 (s106) are also phosphorylated by mapk in vitro and upon stimulation of mapk activity in vivo.Phosphorylation at serines 104 and 106 by erk1/2 mapk is important for estrogen receptor-alpha activity

SIGNOR-156864

Q03112

O15123

1

transcriptional regulation

up-regulates quantity by expression

0.2

We finally observed that the forced expression of Evi1 induced GATA-2 expression in a hematopoietic cell line, EML C1, along with GATA-1, Ang-1, Ang-2 and Tie2

SIGNOR-266060

P52945

P78426

1

transcriptional regulation

up-regulates quantity by expression

0.503

In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1.

SIGNOR-255542

P42574

P98170

0

ubiquitination

down-regulates quantity by destabilization

0.939

Xiap promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.

SIGNOR-109243

O00418

P23443

0

phosphorylation

down-regulates activity

0.736

We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity

SIGNOR-109712

P00519

P12532

1

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we show that oncogenic HER2 tyrosine kinase signaling induces phosphorylation of mitochondrial creatine kinase 1 (MtCK1) on tyrosine 153 (Y153) in an ABL-dependent manner in breast cancer cells. Y153 phosphorylation, which is commonly upregulated in HER2+ breast cancers, stabilizes MtCK1 to increase the phosphocreatine energy shuttle and promote proliferation.

SIGNOR-277406

P06241

P06239

1

phosphorylation

down-regulates activity

0.411

In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.

SIGNOR-279986

O14829

O14737

1

dephosphorylation

down-regulates quantity by destabilization

0.349

Here, we report that the serine/threonine phosphatase PPEF-1 interacts with and dephosphorylates PDCD5 at Ser 119, which leads to PDCD5 destabilization.|These results demonstrate that PPEF-1 reduces PDCD5 stability via PDCD5 dephosphorylation.

SIGNOR-277008

P63000

Q9P107

0

gtpase-activating protein

down-regulates activity

0.445

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-260506

P20336

Q15042

0

gtpase-activating protein

down-regulates activity

0.439

Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).

SIGNOR-265580

Q5U5R9

O75925

1

polyubiquitination

down-regulates quantity by destabilization

0.389

We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model.

SIGNOR-272421

Q9ULT6

O75581

1

ubiquitination

down-regulates quantity

0.656

Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.

SIGNOR-260112

P00352

O14965

0

phosphorylation

up-regulates activity

0.372

AURKA phosphorylates ALDH1A1 at three critical residues which exert a multifaceted regulation over its level, enzymatic activity, and quaternary structure. While all three phosphorylation sites contribute to its increased stability, T267 phosphorylation primarily regulates ALDH1A1 activity. AURKA-mediated phosphorylation rapidly dissociates tetrameric ALDH1A1 into a highly active monomeric species.

SIGNOR-276748

P20393

Q99743

1

transcriptional regulation

down-regulates quantity by repression

0.631

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

SIGNOR-267981

P30304

P20248

1

dephosphorylation

up-regulates activity

0.692

Cdc25A dephosphorylates and activates CyclinE\u2013Cdk2, CyclinA\u2013Cdk2 and CyclinB\u2013Cdk1, whereas Cdc25B and Cdc25C primarily target CyclinB\u2013Cdk1 [4,5] .

SIGNOR-277136

P06730

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.332

This collaborative activity of cIAP1 and CHIP directs eIF4E toward degradation, controlling its levels and suppressing tumorigenesis.|We next sought to investigate whether eIF4E ubiquitination is enhanced by the collaborative activity of cIAP1 and CHIP, which we define as both the E3 ligase activity of cIAP1 alone and the E3 ligase activity of cIAP1 and CHIP together.

SIGNOR-278669

P05198

Q9NR50

0

guanine nucleotide exchange factor

up-regulates activity

0.833

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

SIGNOR-269126

P12931

Q96KB5

1

phosphorylation

up-regulates quantity by stabilization

0.395

Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon

SIGNOR-277217

Q9H3R0

P84243

1

demethylation

down-regulates activity

0.2

As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes.JMJD2C has been proved to be a demethylase for H3K9 methylation, in the manner of catalyzing the demethylation of H3K9me3/me2 (the known repressive markers of gene regulation), a histone mark found in heterochromatin associated with euchromatic transcriptional silencing and heterochromatin formation

SIGNOR-263869

P13807

Q9Y463

0

phosphorylation

down-regulates activity

0.258

DYRK Family Protein Kinases Phosphorylate and Inactivate Glycogen Synthase. both protein kinases phosphorylate site 3a but no other sites that affect glycogen synthase activity.

SIGNOR-260633

O43257

P15173

1

transcriptional regulation

up-regulates quantity by expression

0.259

We show that the srcap subunit named znhit1 or p18hamlet, which is a substrate of p38 mapk, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 mapk-dependent manner. We also show that p18hamlet is required for h2a.z accumulation into this genomic region and for subsequent muscle gene transcriptional activation.

SIGNOR-165613

P09848

Q99626

0

transcriptional regulation

up-regulates quantity by expression

0.362

By electrophoretic mobility-shift assay it was shown that the factor Cdx-2 (a homoeodomain-protein related to caudal) binds to a TTTAC sequence in the CE-LPH1. Furthermore it was demonstrated that Cdx-2 is able to activate reporter gene transcription by binding to CE-LPH1.

SIGNOR-253964

Q8IXI1

O60260

0

polyubiquitination

down-regulates quantity by destabilization

0.2

PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner.

SIGNOR-272726

Q13936

P17612

0

phosphorylation

up-regulates activity

0.498

These findings reveal an essential role for _1C phosphorylation at Ser1928 in stimulating CaV1.2 channel activity and vasoconstriction by AKAP-targeted PKA upon exposure to increased glucose and in diabetes

SIGNOR-251709

P31749

P45983

0

phosphorylation

up-regulates activity

0.427

We report that JNKs are necessary for the reactivation of Akt after ischemic injury. We identified Thr450 of Akt as a residue that is phosphorylated by JNKs, and the phosphorylation status of Thr450 regulates reactivation of Akt after hypoxia, apparently by priming Akt for subsequent phosphorylation by 3-phosphoinositide-dependent protein kinase.

SIGNOR-252426

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

Q92934

Q86V86

0

phosphorylation

down-regulates activity

0.346

Pim kinases phosphorylate multiple sites on Bad and promote 14-3-3 binding and dissociation from Bcl-XL. pim kinases are constitutively active when expressed in HEK-293 cells and are able to phosphorylate the Bcl-2 family member Bad on three residues, Ser112, Ser136 and Ser155 in vitro and in cells.

SIGNOR-250399

P14923

P16591

0

phosphorylation

up-regulates activity

0.526

The tyrosine kinase Fer, which modifies beta-catenin Tyr142, lessening its association with alpha-catenin, phosphorylates plakoglobin Tyr549 and exerts the contrary effect: it raises the binding of plakoglobin to alpha-catenin. Fer stimulation, through modification of Tyr549, causes diminished binding of plakoglobin to components of desmosomes (desmoplakin) and increased interaction with adherens junction proteins (α-catenin)

SIGNOR-251134

O14713

O96013

0

phosphorylation

down-regulates activity

0.2

We further demonstrate that p21 activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser 10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.|We further demonstrate that p21-activated kinase 4 (PAK4) can phosphorylate ICAP1 at Ser-10 both in vitro and in cultured cells, and that active PAK4 inhibits ICAP1 nuclear accumulation in a Ser-10-dependent manner.

SIGNOR-280056

P25490

P07948

0

phosphorylation

down-regulates activity

0.2

In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).

SIGNOR-276930

P60953

Q9H4E7

0

guanine nucleotide exchange factor

up-regulates activity

0.392

Furthermore, membrane targeting of the SLAT Dbl-homology (catalytic) domain was sufficient to trigger TCR-mediated NFAT activation and Th1 and Th2 differentiation in a Cdc42-dependent manner.

SIGNOR-253369

P49841

Q15418

0

phosphorylation

down-regulates

0.359

S6k then phosphorylates the same serine residue on gsk3 that is targeted by pkb/akt (fig. 1), thereby inhibiting its activity.

SIGNOR-110917

Q92974

P28482

0

phosphorylation

up-regulates

0.358

Importantly tnf-alpha enhanced the erk pathway-dependent phosphorylation of thr-678 of gef-h1 that was key for activation.

SIGNOR-184469

Q99704

O14920

0

phosphorylation

up-regulates

0.253

Ikkbeta phosphorylates dok1 s(439)s(443) and s(446)s(450) after tnf-alpha, il-1, or gamma-radiation. mutant dok1 a(439), a(443), a(446), and a(450) differed from wild-type dok1 in not inhibiting platelet-derived growth factor-induced extracellular signal-regulated kinase 1/2 phosphorylation or cell growth. Mutant dok1 a(439), a(443), a(446), and a(450) also did not promote cell motility whereas wild-type dok1 promoted cell motility.

SIGNOR-131447

Q13263

P60510

0

dephosphorylation

down-regulates activity

0.358

PP4 dephosphorylated pKAP1 in vitro.

SIGNOR-277163

Q07666

P06241

0

phosphorylation

up-regulates activity

0.544

The tyrosine kinase Fyn modulates Sam68 mediated alternative splicing of Bcl-x mRNA.|Tyrosine phosphorylation of Sam68 by Fyn inverted this effect and favored the Bcl-x(L) splice site selection.

SIGNOR-279462

P60953

Q07960

0

gtpase-activating protein

down-regulates activity

0.905

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

SIGNOR-260459

Q9NWF9

Q13546

1

ubiquitination

down-regulates quantity by destabilization

0.503

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

SIGNOR-271608

P49840

Q04206

1

phosphorylation

up-regulates activity

0.2

Redundant functions of GSK-3_ and GSK-3_ through phosphorylation of RelA at Thr-254 play a crucial role in early stages of chondrocyte differentiation

SIGNOR-255827

P49841

Q2M1Z3

1

phosphorylation

up-regulates activity

0.302

We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.

SIGNOR-262879

P06213

Q12913

0

dephosphorylation

down-regulates

0.304

Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.

SIGNOR-21295

Q92953

Q9P0L0

1

relocalization

up-regulates quantity

0.2

Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays.|As Kv2.1 accumulates on the surface it begins to bind ER VAPs and form the large and stable membrane junctions.

SIGNOR-262124

Q12959

P11171

0

relocalization

up-regulates activity

0.472

Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.

SIGNOR-266011

Q92630

O95863

1

phosphorylation

down-regulates activity

0.346

DYRK2 mediated Snail degradation protects against tumor cell metastasis.|DYRK2 phosphorylation of Snail at Ser104 triggers sequential phosphorylation by GSK3.

SIGNOR-279328

Q96Q27

P21333

1

polyubiquitination

down-regulates quantity by destabilization

0.442

ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation.

SIGNOR-271740

P00519

Q92993

1

phosphorylation

down-regulates activity

0.647

We present evidence that Tip60 is modified on tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT activity and the subcellular localization of TIP60, which forms a complex with Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association with FE65.

SIGNOR-276598

Q13153

P15336

1

phosphorylation

down-regulates activity

0.2

Overall, our results unequivocally confirmed that Pak1 physically interacts with ATF2 and phosphorylates ATF2 on the Ser62 residue, and this process secludes ATF2 in the cytoplasm.

SIGNOR-279377

P49841

Q9UQB3

1

phosphorylation

down-regulates quantity

0.347

Therefore, our data which supports that partial inhibition of GSK-3beta increases delta-catenin expression, raises an interesting possibility that delta-catenin may be an important downstream target of GSK-3beta signaling that participates in modulating neuronal morphology.|We demonstrate that GSK-3beta forms a stable complex with delta-catenin and phosphorylates delta-catenin in neurons, an event that mediates ubiquitination and subsequent proteasome degradation of delta-catenin.

SIGNOR-279719

Q86VW2

P61586

1

guanine nucleotide exchange factor

up-regulates activity

0.835

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-260544

Q01344

P07948

0

phosphorylation

up-regulates activity

0.475

Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL.|We further delineated that Lyn can induce IL-5RA tyrosine phosphorylation and physically associate with IL-5RA in F/P expressing cells.

SIGNOR-279059

O95835

P11908

1

phosphorylation

down-regulates quantity by destabilization

0.2

Recruitment of TRAF2 to PRPS1/2 requires phosphorylation of PRPS1 S285 or PRPS2 T285, which is mediated by low stiffness-activated large tumor suppressor (LATS)1/2 kinases.LATS1/2-dependent S/T285 phosphorylation is required for PRPS1/2 ubiquitination and degradation at low stiffness.

SIGNOR-276506

Q9UHD2

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.456

Nuclear factor-kappaB activation depends on phosphorylation and degradation of its inhibitor protein, IkapapB. TBK-1 and IKK-i phosphorylate Ser36 of IkappaBalpha.

SIGNOR-246643

Q9H2X6

P16220

1

phosphorylation

up-regulates

0.389

Ere we found that homeodomain-interacting protein kinase 2 (hipk2), a dna-damage responsive nuclear kinase, is a new creb kinase for phosphorylation at ser-271 but not ser-133, and activates creb transactivation function

SIGNOR-166338

Q96A54

P25098

0

phosphorylation

down-regulates activity

0.2

AdipoR1 is Directly Phosphorylated by GRK2.|In summary, our study demonstrates for the first time that cardiometabolic-regulatory, anti-inflammatory, and cardioprotective functions of APN are significantly impaired by GRK2 mediated AdipoR1 phosphorylative desensitization during a critical period of post-MI HF development.

SIGNOR-279463

Q13557

Q08289

1

phosphorylation

up-regulates

0.412

We recently identified ca(v)1.2 beta(2a) residues critical for camkii phosphorylation (thr 498) beta(2a) thr 498 and leu 493 are required for ca(v)1.2 activation by camkii in native cells.

SIGNOR-164067

P49336

P46937

1

phosphorylation

up-regulates activity

0.321

CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.

SIGNOR-277651

Q9P286

Q04206

1

phosphorylation

up-regulates activity

0.2

PAK5-mediated phosphorylation and nuclear translocation of NF-κB-p65 promotes breast cancer cell proliferation in vitro and in vivo|We characterized that PAK5 could promote the phosphorylation and the nuclear translocation of p65 subunit of nuclear factor-kappaB, and demonstrated that p65 could directly bind to the promoter of Cyclin D1

SIGNOR-275657

Q9HA77

P18848

0

transcriptional regulation

up-regulates quantity by expression

0.257

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

SIGNOR-269417

P10586

P06239

1

dephosphorylation

up-regulates

0.364

We confirmed that lar dephosphorylated the phosphorylated tyrosine residues of lck..Activation Of lck and fyn involves tyrosine dephosphorylation of the cooh-terminal regulatory domain of kinases, followed by autophosphorylation of the kinase domain.

SIGNOR-96771

Q4VCS5

O95835

0

phosphorylation

up-regulates quantity by stabilization

0.523

Here low serum and high LATS1 activity are found to enhance the levels of the 130-kDa isoform of angiomotin (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize Amot130

SIGNOR-275843

P27708

P17612

0

phosphorylation

down-regulates

0.307

Protein kinase a phosphorylation at thr456 of the multifunctional protein cad antagonizes activation by the map kinase cascade.

SIGNOR-151816

Q9H6Z4

Q15418

0

phosphorylation

up-regulates quantity

0.319

RSK phosphorylates RanBP3 at Serine 58 residue in vitro and in vivo.RanBP3 phosphorylation increases its affinity towards Ran

SIGNOR-276149

P08047

Q8N695

1

transcriptional regulation

up-regulates quantity by expression

0.2

Luciferase reporter assays of deletion mutants of SLC5A8 promoter demonstrated that a 295-bp region is essential for the basal promoter activity of the SLC5A8 gene. Further analysis indicated that the CCAAT boxes and GC boxes were involved in positive regulation of SLC5A8 promoter. Overexpression of two transcription factors, CCAAT/enhancer binding protein beta (C/EBPbeta) and specific transcription factor 1 (Sp1), upregulated the activities of the human SLC5A8 promoter and protein expression, suggesting that both C/EBPbeta and Sp1 transcription factors might have functions in SLC5A8 transcription.

SIGNOR-254059

P49715

P28845

1

transcriptional regulation

up-regulates quantity by expression

0.274

Cotransfection with human CCAAT/enhancer binding protein-alpha (C/EBPalpha) and C/EBPbeta-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region.

SIGNOR-268971

P19338

P68871

1

post transcriptional regulation

up-regulates quantity by expression

0.2

Nucleolin binds human β-globin mRNA. A Nucleolin-Binding 3′ Untranslated Region Element Stabilizes β-Globin mRNA In Vivo

SIGNOR-251844

P01178-PRO_0000020495

Q92824

0

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270334

Q15831

O14744

1

phosphorylation

up-regulates activity

0.2

We found that PRMT5 is a bona fade substrate for LKB1. We identified T132, 139 and 144 residues, located in the TIM-Barrel domain of PRMT5, as target sites for LKB1 phosphorylation. The point mutation of PRMT5 T139/144 to A139/144 drastically decreased its methyltransferase activity, due probably to the loss of its interaction with regulatory proteins such as MEP50, pICln and RiOK1.

SIGNOR-277412

Q06187

P00519

0

phosphorylation

down-regulates activity

0.336

In this report we describe for the first time that ABL1 and Btk physically interact and that ABL1 can phosphorylate tyrosine 223 in the SH3 domain of Btk. | This is presumably due to the negative regulatory effectof Btk SH3 domain phosphorylation caused by ABL1,which would result in a decreased catalytic activity ofBtk resulting in impaired autophosphorylation.

SIGNOR-260801

P17252

Q9BR76

1

phosphorylation

down-regulates

0.324

We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.

SIGNOR-138733

P04637

Q9UHC7

0

polyubiquitination

down-regulates quantity by destabilization

0.431

Makorin Ring Finger Protein 1 (MKRN1) is a transcriptional co-regulator and an E3 ligase. Here, we show that MKRN1 simultaneously functions as a differentially negative regulator of p53 and p21. In normal conditions, MKRN1 could destabilize both p53 and p21 through ubiquitination and proteasome-dependent degradation. As a result, depletion of MKRN1 induced growth arrest through activation of p53 and p21. K291 and K292 of p53 are required for MKRN1-mediated degradation and ubiquitination of p53

SIGNOR-271846

Q92824

P01178-PRO_0000020496

1

cleavage

up-regulates quantity

0.2

Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.

SIGNOR-270336

P12830

Q9UHD2

0

phosphorylation

down-regulates activity

0.272

Inhibition of TBK1 increases association of Cdh1 with APC1.|It was found that TBK1 phosphorylates both Cdc20 as well as Cdh1 (Figure 2F).

SIGNOR-278996

Q14247

P18031

0

dephosphorylation

up-regulates activity

0.516

We conclude that Mena INV promotes invadopodium maturation by inhibiting normal dephosphorylation of cortactin at tyrosine 421 by the phosphatase PTP1B.

SIGNOR-277027

P49841

O60346

1

phosphorylation

down-regulates

0.353

In addition, we show that the beta-trcp-mediated degradation requires phosphorylation of phlpp1 by casein kinase i and glycogen synthase kinase 3beta (gsk-3beta), and activation of the phosphatidylinositol 3-kinase/akt pathway suppresses the degradation of phlpp1 by inhibiting the gsk-3beta activity.

SIGNOR-188330

P08236

Q9NR19

0

transcriptional regulation

up-regulates quantity by expression

0.262

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy|A chromatin immunoprecipitation (ChIP) assay with antibodies against TFEB or ACSS2 demonstrated that glucose deprivation results in the binding of TFEB (Figure 3D) and ACSS2 (Figure 3E) to the promoter regions of CTSA, GBA, GUSB, and LAMP1|These results indicated that TFEB and ACSS2 are mutually required for their binding to the promoter regions of lysosomal genes. In line with these findings, glucose deprivation induced mRNA (Figure 3F) and protein (Figure 3G) expression for these lysosomal genes, which was largely abrogated by knockin of ACSS2 mutants

SIGNOR-276554

P28482

P04637

1

phosphorylation

up-regulates activity

0.778

In summary, our results suggest that phosphorylation of p53Thr55 by ERK2 is important for doxorubicin-induced p53 activation and cell death.

SIGNOR-279068

Q6ZVD8

P17252

1

dephosphorylation

down-regulates quantity

0.253

In addition, knockdown of PHLPP expression reduces the rate of phorbol ester-triggered dephosphorylation of the hydrophobic motif, but not turn motif, of PKC alpha

SIGNOR-237051

P18031

P12931

1

dephosphorylation

up-regulates activity

0.781

Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-419 and of Tyr-530

SIGNOR-245299

P07948

P25490

1

phosphorylation

down-regulates activity

0.2

In the case of Lyn overexpression, single mutations at either tyrosine 8, 254, or 383 severely reduced Lyn-mediated YY1 phosphorylation, suggesting that these three sites may be targets of Lyn in vivo (Fig. 3, A and B).

SIGNOR-276930