GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
Q13882	Q6P1J9	1	phosphorylation	down-regulates activity	0.368	PTK6 impairs the coactivator function of parafibromin.\|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.	SIGNOR-279273
P29320	P10275	1	phosphorylation	up-regulates activity	0.273	These data suggest that Etk may be able to phosphorylate AR at Y534 and Y551/552, and the interaction between the Etk SH2 domain and phosphorylated ARY551/552 may promote their association.\|This is supported by our observations that the association between Etk and AR is increased after castration and Etk induces tyrosine phosphorylation of AR, leading an increase in AR stability and transcriptional activity under androgen depleted conditions.	SIGNOR-279371
Q9NZI8	P60709	1	post transcriptional regulation	up-regulates quantity	0.34	We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.	SIGNOR-268160
Q14576	O14672	1	post transcriptional regulation	up-regulates quantity	0.2	Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure	SIGNOR-266864
P62714	Q00987	1	dephosphorylation	up-regulates activity	0.4	cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells	SIGNOR-248593
P12931	P01135	1	cleavage	up-regulates	0.3	Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.	SIGNOR-235888
O00429	Q5S007	0	phosphorylation	up-regulates activity	0.568	LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy	SIGNOR-276495
P12931	O15259	1	phosphorylation	up-regulates activity	0.297	Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721.	SIGNOR-279122
Q9HAU4	P36897	1	polyubiquitination	down-regulates quantity by destabilization	0.71	Smad7 Recruits Smurf2 to the TGFβ Receptor Complex. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways.	SIGNOR-272938
O60548	P10644	1	transcriptional regulation	up-regulates quantity by expression	0.2	Elevating the amounts of FOXD2 expression vector up to 12-fold relative to the RIα1b reporter construct demonstrated that maximal induction of the RIα1b promoter by FOXD2 was at least 5.8-fold	SIGNOR-261605
P20963	P06239	0	phosphorylation	up-regulates	0.764	During tcr signaling, lck interacts with numerous molecules, including tcr-zeta. The binding of lck to the tyrosine-phosphorylated zeta chain of the tcr would serve to strengthen the interaction of the associated cd4 and the tcr complex, leading to increased avidity for the antigen-major histocompatibility protein complex.	SIGNOR-41361
Q13813	P12931	0	phosphorylation	up-regulates	0.563	Using mutagenesis on recombinant peptides, we identified the residue y1176 located in the calpain cleavage site of alpha ii-spectrin, near the sh3 domain, as an in vitro substrate for src kinase and lmw-ptp a. phosphorylation of this residue decreases spectrin sensitivity to calpain in vitro.	SIGNOR-86718
Q8IWV1	P43405	0	phosphorylation	up-regulates activity	0.378	Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.	SIGNOR-273535
O14733	P45984	1	phosphorylation	up-regulates	0.637	Here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1). These results indicate that hgk, a novel activator of the jnk pathway, may function through tak1, and that the hgk --> tak1 --> mkk4, mkk7 --> jnk kinase cascade may mediate the TNF-alphalpha signaling pathway.	SIGNOR-83744
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
P08237	O15294	0	glycosylation	down-regulates activity	0.346	Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity\|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.	SIGNOR-267584
Q99814	Q6ZMT4	1	transcriptional regulation	up-regulates quantity by expression	0.2	To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.	SIGNOR-271587
Q96PY6	P21796	1	phosphorylation	down-regulates	0.424	Nek1 phosphorylates vdac1 on ser193. Wild-type vdac1 assumes an open configuration, but closes and prevents cytochrome c efflux when phosphorylated by nek1. A vdac1-ser193ala mutant, which cannot be phosphorylated by nek1 under identical conditions, remains open and constitutively allows cytochrome c efflux.	SIGNOR-164222
P63000	P11274	0	gtpase-activating protein	down-regulates activity	0.601	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-260526
P17252	P43629	1	phosphorylation	down-regulates activity	0.2	Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII.	SIGNOR-276080
Q9BXW9	O94782	0	deubiquitination	down-regulates activity	0.761	The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2\|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells	SIGNOR-263273
P28324	Q9Y5U4	1	transcriptional regulation	up-regulates quantity by expression	0.2	Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.	SIGNOR-261592
Q14493	P68400	0	phosphorylation	down-regulates quantity by destabilization	0.328	Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation.	SIGNOR-265260
Q9UKT4	P06493	0	phosphorylation	down-regulates quantity by destabilization	0.753	We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction.	SIGNOR-279143
P48729	Q04206	1	phosphorylation	up-regulates activity	0.2	These data strongly suggested that CKI phosphorylated Ser-316 of p65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation.	SIGNOR-276916
Q5VST9	P52179	0	relocalization	up-regulates quantity	0.3	Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.	SIGNOR-266727
P05186	P10636	1	dephosphorylation	down-regulates activity	0.2	TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death.	SIGNOR-277097
P14778	P45983	1	phosphorylation	up-regulates activity	0.379	Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab	SIGNOR-249513
P06239	P06241	0	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
Q96CN9	Q15811	1	relocalization	up-regulates activity	0.2	GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).	SIGNOR-260600
P53805	O43318	0	phosphorylation	up-regulates activity	0.2	Here we showed that TAK1 directly phosphorylated RCAN1 at two novel sites (serine 94 and -136), resulting in activation of calcineurin-NFAT signaling.\|Indeed, low doses of RCAN1 facilitated calcineurin-nuclear factor of activated T cells signaling in the presence of TGF-\u03b2-activated kinase 1+TAB1 ( ), suggesting that TGF-\u03b2-activated kinase 1 augments calcineurin-nuclear factor of activated T cells signaling through RCAN1.	SIGNOR-279535
Q04206	P01584	1	transcriptional regulation	down-regulates activity	0.555	Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide\|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages	SIGNOR-251736
P43250	P25025	1	phosphorylation	down-regulates quantity	0.563	GRK2 mainly phosphorylates CXCR1, while GRK6 mediates CXCR2 phosphorylation .\|Overexpression of GRK6 or treatment with CXCR2 siRNA suppresses CXCR2 expression in dorsal root ganglion and significantly reduces pain in animal model of neuropathic pain , .	SIGNOR-279782
P19429	Q13976	0	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
Q9UBS0	O15530	0	phosphorylation	up-regulates activity	0.609	Mutational analysis revealed that the phosphorylation of Thr241 and Thr401 in p70beta1 was indispensable for the kinase activity. In contrast, a p70beta1 mutant in which Ser383 was substituted with Gly (S383G) still retained nearly the half maximal activity. Sequential phosphorylation of wild-type and S383G mutant of p70beta1 with mTOR and 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro synergistically activated their kinase activities.	SIGNOR-250272
Q8NER1	P29350	0	dephosphorylation	down-regulates activity	0.2	Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.\|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.	SIGNOR-277129
O43623	P49841	0	phosphorylation	down-regulates activity	0.423	GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP mediated degradation of Slug.\|Phosphorylation of Slug by GSK3beta promotes CHIP binding and ubiquitin mediated proteolysis.	SIGNOR-279414
P68400	P18846	1	phosphorylation	up-regulates	0.296	Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site	SIGNOR-42565
P26927	P17252	1	phosphorylation	up-regulates activity	0.2	Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.	SIGNOR-277179
Q13118	P24941	0	phosphorylation	up-regulates quantity	0.329	In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .\|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.	SIGNOR-278394
Q03135	P08581	0	phosphorylation	up-regulates activity	0.424	Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.\|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.	SIGNOR-279080
Q6ZVD8	P31749	1	dephosphorylation	down-regulates	0.773	Here, we identify a protein phosphatase, ph domain leucine-rich repeat protein phosphatase (phlpp), that specifically dephosphorylates the hydrophobic motif of akt (ser473 in akt1), triggering apoptosis and suppressing tumor growth.[...] These data are consistent with phlpp terminating akt signaling by directly dephosphorylating and inactivating akt.	SIGNOR-252602
P12259	P00734	0	null	up-regulates activity	0.882	Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind	SIGNOR-263530
P46937	Q05513	0	phosphorylation	down-regulates quantity by destabilization	0.277	Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation.	SIGNOR-276877
O60260	P49792	1	ubiquitination	down-regulates quantity by destabilization	0.2	Our findings suggested that the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways. Furthermore, Parkin controls the intracellular levels of sumoylated HDAC4, as a result of the ubiquitination and degradation of RanBP2.	SIGNOR-259116
P16104	Q13315	0	phosphorylation	up-regulates	0.2	H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.	SIGNOR-160206
Q9UBE8	P15884	1	phosphorylation	down-regulates	0.2	Whereas lef-1 and tcf-4 phosphorylation by nlk (nemo-like kinase) leads to less lef/tcf/beta-catenin complex binding to dna and to lef-1/tcf-4 degradation	SIGNOR-24147
P18848	P49589	1	transcriptional regulation	up-regulates quantity by expression	0.2	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-269416
P00519	Q13671	1	phosphorylation	up-regulates	0.751	We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.	SIGNOR-48142
P23470	Q06187	1	dephosphorylation	down-regulates activity	0.262	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254694
P24752	P08559	1	acetylation	down-regulates activity	0.393	We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)	SIGNOR-267633
Q7Z419	P06748	1	ubiquitination	down-regulates quantity by destabilization	0.2	NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells	SIGNOR-271490
Q96EB6	Q02577	1	deacetylation	up-regulates activity	0.383	SIRT1 deacetylates the brain-specific helix-loop-helix transcription factor NHLH2 on lysine 49 to increase its activation of the MAO-A promoter	SIGNOR-254830
Q9P0U3	Q9NP62	1	desumoylation	up-regulates activity	0.468	We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.	SIGNOR-262681
Q8IW19	Q13315	0	phosphorylation	up-regulates activity	0.4	We show that APLF undergoes ATM dependent hyperphosphorylation following IR and that APLF is directly phosphorylated by ATM in vitro.	SIGNOR-279492
Q9BW19	Q13535	0	phosphorylation	up-regulates quantity by stabilization	0.257	ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro.	SIGNOR-277296
P62136	P30281	1	dephosphorylation	up-regulates	0.246	These results support the hypothesis that pp1 constitutively keeps cyclin d3 in a stable, dephosphorylated state	SIGNOR-142884
O14920	Q04864	1	phosphorylation	up-regulates activity	0.62	We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.	SIGNOR-279620
Q9P0L9	Q9UQM7	0	phosphorylation	down-regulates activity	0.2	CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3.	SIGNOR-277812
P68400	Q01082	1	phosphorylation	down-regulates	0.334	We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.	SIGNOR-150471
A6NJ46	Q9NS71	1	transcriptional regulation	up-regulates quantity by expression	0.371	In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.	SIGNOR-266096
P49840	P31751	0	phosphorylation	down-regulates	0.557	Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3	SIGNOR-138179
P49841	Q92585	1	phosphorylation	down-regulates	0.2	We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1	SIGNOR-187896
P30304	P14618	1	dephosphorylation	up-regulates activity	0.487	Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.\|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.	SIGNOR-276967
Q38SD2	Q96SN8	1	phosphorylation	up-regulates activity	0.505	Interestingly, LRRK1 in turn phosphorylates CDK5RAP2(Cep215), a human homologue of Drosophila Centrosomin (Cnn), in its gamma-tubulin-binding motif, thus promoting the interaction of CDK5RAP2 with gamma-tubulin. LRRK1 phosphorylation of CDK5RAP2 Ser 140 is necessary for CDK5RAP2-dependent microtubule nucleation.	SIGNOR-275468
P00519	Q06124	1	phosphorylation	up-regulates activity	0.374	Direct phosphorylation of SHP-2 by Abl kinases (Y580) promotes sustained activation of SHP-2 signaling and proliferation, and c-Abl/Abl-Related Gene-dependent activation of tyrosine kinase X further potentiates SHP-2 signaling by phosphorylating SHP-2 on Y63.\|Endogenous Abl kinases phosphorylate SHP-2 on Y580 and induce sustained ERK phosphorylation in response to PDGF.	SIGNOR-278217
P31749	O60825	1	phosphorylation	up-regulates activity	0.654	These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor.	SIGNOR-252555
P53355	Q16623	1	phosphorylation	down-regulates activity	0.339	Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking.	SIGNOR-251083
P60953	Q9NYF5	0	gtpase-activating protein	down-regulates activity	0.452	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-260504
P49841	Q6U7Q0	1	phosphorylation	down-regulates quantity by destabilization	0.2	CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction.	SIGNOR-264891
A7KAX9	Q13480	0	relocalization	up-regulates	0.314	Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2.	SIGNOR-102586
Q12913	P09619	1	dephosphorylation	down-regulates activity	0.582	Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1\|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021	SIGNOR-248704
P41743	P15311	1	phosphorylation	up-regulates	0.342	Pkciota phosphorylated ezrin on t567 in vitro, and in sf9 cells that do not activate human ezrin. we conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by pkciota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.	SIGNOR-160855
P54646	Q9UQB8	1	phosphorylation	down-regulates	0.2	Using this approach for ppp1r12c, baiap2, and cdc27, we found that mutation of a single serine to alanine (s452, s366, and s379 respectively) resulted in almost a complete loss of ampk phosphorylation in these proteins. Termination of irsp53 function is suggested to occur following cdc42 dissociation, kinase phosphorylation of t340 and t360, and subsequent 14-3-3 binding, which competes for sh3 partners, thus allowing filopodial retraction	SIGNOR-195102
P27361	P00533	1	phosphorylation	down-regulates	0.557	It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.	SIGNOR-20549
P12931	A1X283	1	phosphorylation	up-regulates activity	0.521	C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells\|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.	SIGNOR-264705
P49674	Q9UJU2	1	phosphorylation	down-regulates	0.268	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-134497
O95140	Q9UKV5	0	polyubiquitination	down-regulates quantity by destabilization	0.3	Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2.	SIGNOR-272887
Q99550	Q6IQ55	0	phosphorylation	down-regulates quantity	0.2	Additionally, in vivo ubiquitin assays showed that expression of either the kinase-dead TTBK2 or the MPP9-S629 and S636-2A mutant significantly decreased the ubiquitination level of MPP9.\|Also, the S629A mutant almost abolished the phosphorylation of MPP9 by TTBK2 in the kinase assay in vitro, suggesting that S629 is the main site for MPP9 phosphorylation by TTBK2.	SIGNOR-278998
Q05513	Q16612	1	phosphorylation	down-regulates quantity by destabilization	0.2	Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.	SIGNOR-273831
P78362	P31749	0	phosphorylation	up-regulates	0.465	Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.	SIGNOR-186760
Q03135	O60260	0	ubiquitination	down-regulates quantity	0.2	Parkin induces the degradation of cav-1 through the proteasome dependent pathway.\|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.	SIGNOR-278710
Q13043	Q12778	1	phosphorylation	up-regulates	0.595	Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1.	SIGNOR-191847
P78411	Q9NZV8	1	transcriptional regulation	down-regulates quantity by repression	0.487	Irx5 Directly Represses the Kcnd2 Promoter	SIGNOR-266045
Q96LC9	P45983	0	phosphorylation	up-regulates activity	0.689	Activated JNK causes BimL and Bmf phosphorylation in vivo. It is known that UV radiation causes the release of Bim and Bmf from dynein and myosin V motor complexes and that these proteins cause Bax/Bak-dependent apoptosis . The results of this study demonstrate that JNK can engage this apoptotic pathway by phosphorylation of BH3-only proteins, including Bim and Bmf.	SIGNOR-250116
O95292	Q92953	0	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-262123
Q07820	Q9Y577	0	polyubiquitination	down-regulates quantity by destabilization	0.444	Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.	SIGNOR-272032
Q13191	P36888	1	ubiquitination	down-regulates activity	0.326	Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.	SIGNOR-260106
O15379	P49327	1	deacetylation	up-regulates quantity by stabilization	0.2	Overexpression of HA-HDAC3 decreased the acetylation level of endogenous FASN by 35% in HEK293T cells, while the expression of a catalytic inactive mutant HDAC3Y298H (38) failed to reduce FASN acetylation (Fig. 4C). Conversely, HDAC3 knockdown increased the acetylation level of endogenous FASN by >1.5-fold in HEK293T cells	SIGNOR-267367
Q07912	P31749	1	phosphorylation	up-regulates activity	0.427	Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.	SIGNOR-252446
P45983	P05412	1	phosphorylation	up-regulates activity	0.907	JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain.	SIGNOR-250122
Q9NQU5	P08134	1	phosphorylation	down-regulates activity	0.2	It is possible that Pak6 may directly phosphorylate RhoC to regulate its activity.\|Nevertheless, our results clearly show that the kinase activity of Pak6 is required to inhibit RhoC induced cell contraction.	SIGNOR-280059
P00734	P00451	1	cleavage	up-regulates activity	0.755	Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689.	SIGNOR-263640
P05771	Q99418	1	phosphorylation	down-regulates activity	0.307	ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.	SIGNOR-249024
Q14493	Q16778	1	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265386
Q9UBE8	O43318	0	phosphorylation	up-regulates	0.651	The tak1-nlk-mapk-related pathway antagonizes signalling between beta-catenin and transcription factor tcf.	SIGNOR-96425
Q13153	Q02750	1	phosphorylation	up-regulates activity	0.582	We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation.	SIGNOR-236002
P08246	P05546	1	cleavage	down-regulates activity	0.451	Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.	SIGNOR-256510
Q96SB4	P53671	0	phosphorylation	up-regulates activity	0.2	In vitro kinase assays revealed that LIMK2 phosphorylates SRPK1 (Fig. xref ).\|LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.	SIGNOR-279625
Q8NFU7	Q96SR6	1	transcriptional regulation	up-regulates quantity by expression	0.2	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259095

Q13882

Q6P1J9

1

phosphorylation

down-regulates activity

0.368

PTK6 impairs the coactivator function of parafibromin.|To study the functional consequence of parafibromin phosphorylation by PTK6, we examined the effect of PTK6 inhibition on Wnt signal activation.

SIGNOR-279273

P29320

P10275

1

phosphorylation

up-regulates activity

0.273

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

SIGNOR-279371

Q9NZI8

P60709

1

post transcriptional regulation

up-regulates quantity

0.34

We found that ZBP1 is necessary for netrin-1 stimulated local translation of β-actin mRNA in axonal growth cones. ZBP1 binds to β-actin mRNA in the soma and transports it to the growth cone on microtubules.

SIGNOR-268160

Q14576

O14672

1

post transcriptional regulation

up-regulates quantity

0.2

Neuronal ELAV (nELAV) proteins are RNA-binding proteins which play a physiological role in controlling gene expression in memory formation, and their alteration may contribute to cognitive impairment associated with neurodegenerative pathologies such as Alzheimer's disease (AD). The experiments show for the first time that ADAM10mRNA represents a nELAV target and that these RNA-binding proteins can play a role in the post-transcriptional regulation of ADAM10 expression. nELAV proteins specifically bind the ADAM10 mRNA and this binding is disrupted following Aβ exposure

SIGNOR-266864

P62714

Q00987

1

dephosphorylation

up-regulates activity

0.4

cyclin G also binds in vivo and in vitro to Mdm2 and markedly stimulates the ability of PP2A to dephosphorylate Mdm2 at T216. Consistent with these data, cyclin G null cells have both Mdm2 that is hyperphosphorylated at T216 and markedly higher levels of p53 protein when compared to wild-type cells

SIGNOR-248593

P12931

P01135

1

cleavage

up-regulates

0.3

Ep2 can also promote the transactivation of epidermal growth factor receptor (egfr) expressed in colon cancer cells through src, which activates the proteolytic release of the egfr ligands amphiregulin (ar) and transforming growth factor-alfa (tgfalfa)125, thereby stimulating the egfr- network.

SIGNOR-235888

O00429

Q5S007

0

phosphorylation

up-regulates activity

0.568

LRRK2 G2019S directly bound to and phosphorylated Drp1 at Threonine595, whereas P110 treatment abolished this phosphorylation.Threonine595 phosphorylation of Drp1 by LRRK2 G2019S is required for Drp1-mediated mitochondrial fragmentation and excessive autophagy

SIGNOR-276495

P12931

O15259

1

phosphorylation

up-regulates activity

0.297

Src-induced tyrosine phosphorylation could be prevented by mutating the tyrosine residue at position 721 to phenylalanine ( C, lane 12) suggesting that Src kinase phosphorylates NPHP1 at tyrosine 721.

SIGNOR-279122

Q9HAU4

P36897

1

polyubiquitination

down-regulates quantity by destabilization

0.71

Smad7 Recruits Smurf2 to the TGFβ Receptor Complex. Here, we identify Smurf2, a C2-WW-HECT domain ubiquitin ligase and show that Smurf2 associates constitutively with Smad7. Smurf2 is nuclear, but binding to Smad7 induces export and recruitment to the activated TGF beta receptor, where it causes degradation of receptors and Smad7 via proteasomal and lysosomal pathways.

SIGNOR-272938

O60548

P10644

1

transcriptional regulation

up-regulates quantity by expression

0.2

Elevating the amounts of FOXD2 expression vector up to 12-fold relative to the RIα1b reporter construct demonstrated that maximal induction of the RIα1b promoter by FOXD2 was at least 5.8-fold

SIGNOR-261605

P20963

P06239

0

phosphorylation

up-regulates

0.764

During tcr signaling, lck interacts with numerous molecules, including tcr-zeta. The binding of lck to the tyrosine-phosphorylated zeta chain of the tcr would serve to strengthen the interaction of the associated cd4 and the tcr complex, leading to increased avidity for the antigen-major histocompatibility protein complex.

SIGNOR-41361

Q13813

P12931

0

phosphorylation

up-regulates

0.563

Using mutagenesis on recombinant peptides, we identified the residue y1176 located in the calpain cleavage site of alpha ii-spectrin, near the sh3 domain, as an in vitro substrate for src kinase and lmw-ptp a. phosphorylation of this residue decreases spectrin sensitivity to calpain in vitro.

SIGNOR-86718

Q8IWV1

P43405

0

phosphorylation

up-regulates activity

0.378

Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85.

SIGNOR-273535

O14733

P45984

1

phosphorylation

up-regulates

0.637

Here we report that mkk4 shows a striking preference for the tyrosine residue (tyr-185), and mkk7 a striking preference for the threonine residue (thr-183) in three sapk1/jnk1 isoforms tested (jnk1 alpha 1, jnk2 alpha 2 and jnk3 alpha 1). These results indicate that hgk, a novel activator of the jnk pathway, may function through tak1, and that the hgk --> tak1 --> mkk4, mkk7 --> jnk kinase cascade may mediate the TNF-alphalpha signaling pathway.

SIGNOR-83744

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

P08237

O15294

0

glycosylation

down-regulates activity

0.346

Our previous investigation on O-GlcNAcylation of PFK1 has demonstrated that O-GlcNAcylation inhibits PFK1 enzyme activity|In cells, a single set of antagonistic enzymes-O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase are responsible for the addition and removal of GlcNAc moiety, respectively.

SIGNOR-267584

Q99814

Q6ZMT4

1

transcriptional regulation

up-regulates quantity by expression

0.2

To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.

SIGNOR-271587

Q96PY6

P21796

1

phosphorylation

down-regulates

0.424

Nek1 phosphorylates vdac1 on ser193. Wild-type vdac1 assumes an open configuration, but closes and prevents cytochrome c efflux when phosphorylated by nek1. A vdac1-ser193ala mutant, which cannot be phosphorylated by nek1 under identical conditions, remains open and constitutively allows cytochrome c efflux.

SIGNOR-164222

P63000

P11274

0

gtpase-activating protein

down-regulates activity

0.601

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-260526

P17252

P43629

1

phosphorylation

down-regulates activity

0.2

Functional studies of the wild-type receptor and serine/threonine mutants indicated that phosphorylation of Ser(394) by protein kinase C slightly suppresses KIR3DL1 inhibitory function, and reduces receptor internalization and turnover.Both CKII and PKC phosphorylate KIR3DL1 in vitro. Ser364 can be phosphorylated after phosphorylation of Ser367 by CKII.

SIGNOR-276080

Q9BXW9

O94782

0

deubiquitination

down-regulates activity

0.761

The deubiquitinating enzyme USP1 controls the cellular levels of the DNA damage response protein Ub-FANCD2|The level of monoubiquitinated FANCD2 protein increases in response to various types of DNA damage in mammalian cells

SIGNOR-263273

P28324

Q9Y5U4

1

transcriptional regulation

up-regulates quantity by expression

0.2

Under these conditions, a significant reduction in INSIG2 expression was only observed when SAP1a siRNA was used. These observations provide supporting evidence that SAP1a may be one of the transactivators of the human INSIG2 promoter.

SIGNOR-261592

Q14493

P68400

0

phosphorylation

down-regulates quantity by destabilization

0.328

Phosphorylation of Thr61 is necessary for subsequent phosphorylation of Thr60 by CK2 in vitro. Inhibitors of CK2 also prevent degradation of SLBP at the end of S phase. Thus, phosphorylation of Thr61 by cyclin A/Cdk1 primes phosphorylation of Thr60 by CK2 and is responsible for initiating SLBP degradation.

SIGNOR-265260

Q9UKT4

P06493

0

phosphorylation

down-regulates quantity by destabilization

0.753

We find that both Emi1 phosphorylation by cyclin and Cdc2 and phosphorylation on a consensus site (DSGxxS) direct recruitment of betaTrCP and subsequent Emi1 ubiquitination and destruction.

SIGNOR-279143

P48729

Q04206

1

phosphorylation

up-regulates activity

0.2

These data strongly suggested that CKI phosphorylated Ser-316 of p65. Our data suggested that phosphorylation of p65 on Ser-316 controls the activity and function of NF-κB. Importantly, we found that phosphorylation at the novel Ser-316 site and other two known phosphorylation sites, Ser-529 and Ser-536, either individually or cooperatively, regulated distinct groups of NF-κB-dependent genes, suggesting the unique role of each individual phosphorylation site on NF-κB-dependent gene regulation.

SIGNOR-276916

Q5VST9

P52179

0

relocalization

up-regulates quantity

0.3

Ankyrin-B is targeted to the M-line via its interaction with the C-terminal domain of the large sarcomeric protein obscurin. Obscurin is targeted to the M-line via its N-terminal interactions with myomesin and titin. This population of ankyrin-B recruits B56α, a regulatory subunit of protein phosphatase 2A, to the M-line where the phosphatase may regulate the phosphorylation status of contractile and signalling proteins.

SIGNOR-266727

P05186

P10636

1

dephosphorylation

down-regulates activity

0.2

TNAP dephosphorylates overphosphorylated tau once it is released upon neuronal death.

SIGNOR-277097

P14778

P45983

1

phosphorylation

up-regulates activity

0.379

Il-1 binding to its receptor triggers a cascade of signaling events, including activation of the stress-activated mitogen-activated protein (map) kinases, c-jun nh2-terminal kinase (jnk) and p38 map kinase, as well as transcription factor nuclear factor kappab (nf-kappab

SIGNOR-249513

P06239

P06241

0

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

Q96CN9

Q15811

1

relocalization

up-regulates activity

0.2

GFP-GCC88 was immunoprecipitated by both the short and long form of ITSN-1 but not with FLAG-Rheb (Figure 4A). These data demonstrate that both GCC88 and ITSN-1 are part of a complex. We propose that GCC88 recruits ITSN-1-L to the TGN, which in turn activates Cdc42 at the trans-face of the Golgi (Figure 9A).

SIGNOR-260600

P53805

O43318

0

phosphorylation

up-regulates activity

0.2

Here we showed that TAK1 directly phosphorylated RCAN1 at two novel sites (serine 94 and -136), resulting in activation of calcineurin-NFAT signaling.|Indeed, low doses of RCAN1 facilitated calcineurin-nuclear factor of activated T cells signaling in the presence of TGF-\u03b2-activated kinase 1+TAB1 ( ), suggesting that TGF-\u03b2-activated kinase 1 augments calcineurin-nuclear factor of activated T cells signaling through RCAN1.

SIGNOR-279535

Q04206

P01584

1

transcriptional regulation

down-regulates activity

0.555

Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages

SIGNOR-251736

P43250

P25025

1

phosphorylation

down-regulates quantity

0.563

GRK2 mainly phosphorylates CXCR1, while GRK6 mediates CXCR2 phosphorylation .|Overexpression of GRK6 or treatment with CXCR2 siRNA suppresses CXCR2 expression in dorsal root ganglion and significantly reduces pain in animal model of neuropathic pain , .

SIGNOR-279782

P19429

Q13976

0

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

Q9UBS0

O15530

0

phosphorylation

up-regulates activity

0.609

Mutational analysis revealed that the phosphorylation of Thr241 and Thr401 in p70beta1 was indispensable for the kinase activity. In contrast, a p70beta1 mutant in which Ser383 was substituted with Gly (S383G) still retained nearly the half maximal activity. Sequential phosphorylation of wild-type and S383G mutant of p70beta1 with mTOR and 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro synergistically activated their kinase activities.

SIGNOR-250272

Q8NER1

P29350

0

dephosphorylation

down-regulates activity

0.2

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.|These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.

SIGNOR-277129

O43623

P49841

0

phosphorylation

down-regulates activity

0.423

GSK3beta controls epithelial-mesenchymal transition and tumor metastasis by CHIP mediated degradation of Slug.|Phosphorylation of Slug by GSK3beta promotes CHIP binding and ubiquitin mediated proteolysis.

SIGNOR-279414

P68400

P18846

1

phosphorylation

up-regulates

0.296

Camk ii phosphorylates only ser63 (corresponding to ser133 of creb), which is essential for the activation, and not ser72 (corresponding to ser142 of creb), which is a negative regulation site

SIGNOR-42565

P26927

P17252

1

phosphorylation

up-regulates activity

0.2

Thus, the phosphorylation of PKCα at Ser226 and Thr228 by Mst1 and Mst2 is required for the optimal activation of PKCα.

SIGNOR-277179

Q13118

P24941

0

phosphorylation

up-regulates quantity

0.329

In this study we have shown that CDK2 phosphorylates KLF10 at residue Ser 206 in vivo and in vitro .|In this study, we have shown that KLF10 protein has tightly controlled expression and that the expression level varies in a cell cycle dependent manner whereby CDK2 up-regulates activity the protein level of KLF10 through interference with the protein 's association with SIAH1.

SIGNOR-278394

Q03135

P08581

0

phosphorylation

up-regulates activity

0.424

Findings obtained using SNU-449 cells suggested that c-Met positively regulated CAV1 activity.|Inhibition of c-Met activation abolished phosphorylation of CAV1 on Tyrosine 14.

SIGNOR-279080

Q6ZVD8

P31749

1

dephosphorylation

down-regulates

0.773

Here, we identify a protein phosphatase, ph domain leucine-rich repeat protein phosphatase (phlpp), that specifically dephosphorylates the hydrophobic motif of akt (ser473 in akt1), triggering apoptosis and suppressing tumor growth.[...] These data are consistent with phlpp terminating akt signaling by directly dephosphorylating and inactivating akt.

SIGNOR-252602

P12259

P00734

0

null

up-regulates activity

0.882

Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind

SIGNOR-263530

P46937

Q05513

0

phosphorylation

down-regulates quantity by destabilization

0.277

Yap and β-catenin are direct substrates of PKCζ.We show here that PKCζ suppresses intestinal stem cell function by promoting the downregulation of β-catenin and Yap through direct phosphorylation.Consistent with MS/MS analysis, mutation to alanine of these two sites completely abolished Yap phosphorylation by PKCζ. Interestingly, S109 and T110 sites were highly conserved among species (Figure S3B), which suggested an important role in Yap regulation.

SIGNOR-276877

O60260

P49792

1

ubiquitination

down-regulates quantity by destabilization

0.2

Our findings suggested that the intracellular levels of RanBP2 and its functional activity may be modulated by Parkin-mediated ubiquitination and proteasomal pathways. Furthermore, Parkin controls the intracellular levels of sumoylated HDAC4, as a result of the ubiquitination and degradation of RanBP2.

SIGNOR-259116

P16104

Q13315

0

phosphorylation

up-regulates

0.2

H2ax interacts with numerous proteins required for dna damage signaling and repair when phosphorylated on ser-140. Phosphorylation of ser-140 (h2ax139ph) in response to ionizing radiation is mediated by both atm and prkdc. Our data showed that h2ax is phosphorylated by uva-activated jnk.

SIGNOR-160206

Q9UBE8

P15884

1

phosphorylation

down-regulates

0.2

Whereas lef-1 and tcf-4 phosphorylation by nlk (nemo-like kinase) leads to less lef/tcf/beta-catenin complex binding to dna and to lef-1/tcf-4 degradation

SIGNOR-24147

P18848

P49589

1

transcriptional regulation

up-regulates quantity by expression

0.2

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-269416

P00519

Q13671

1

phosphorylation

up-regulates

0.751

We also report that the amino-terminal domain of rin1 contains sequences that can mediate interactions with the abl tyrosine kinase and that rin1 is itself tyrosine phosphorylated by c-abl.

SIGNOR-48142

P23470

Q06187

1

dephosphorylation

down-regulates activity

0.262

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254694

P24752

P08559

1

acetylation

down-regulates activity

0.393

We previously reported that the mitochondrial fraction of FLT3 activates acetyl-CoA acetyltransferase ACAT1 in mitochondria via Y407 phosphorylation to acetylate and inhibit mitochondrial pyruvate dehydrogenase A (PDHA) and PDH phosphatase 1 (PDP1)

SIGNOR-267633

Q7Z419

P06748

1

ubiquitination

down-regulates quantity by destabilization

0.2

NPMc degradation was mediated by the ubiquitin-proteasome pathway involving the IBR-type RING-finger E3 ubiquitin ligase IBRDC2, and genetic correction of FA-A or FA-C lymphoblasts prevented NPMc ubiquitination. As shown in Fig. 4C, knockdown of IBRDC2, an IBR-type RING-finger E3 ubiquitin ligase (21), significantly reduced NPMc ubiquitination and restored NPMc stability in FA-A cells

SIGNOR-271490

Q96EB6

Q02577

1

deacetylation

up-regulates activity

0.383

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

SIGNOR-254830

Q9P0U3

Q9NP62

1

desumoylation

up-regulates activity

0.468

We show that Epac1 and Rap1, in response to cAMP, activate CaMKI to phosphorylate Ser47 in GCM1. This phosphorylation facilitates the interaction between GCM1 and the desumoylating enzyme SENP1 and thereby leads to GCM1 desumoylation and activation.

SIGNOR-262681

Q8IW19

Q13315

0

phosphorylation

up-regulates activity

0.4

We show that APLF undergoes ATM dependent hyperphosphorylation following IR and that APLF is directly phosphorylated by ATM in vitro.

SIGNOR-279492

Q9BW19

Q13535

0

phosphorylation

up-regulates quantity by stabilization

0.257

ATM and ATR kinases phosphorylate KIFC1-S26 during DNA-damage conditions.KIFC1 was stabilized upon phosphorylation and thus promoted centrosome clustering, CIN, and tumor recurrence both in vivo and in vitro.

SIGNOR-277296

P62136

P30281

1

dephosphorylation

up-regulates

0.246

These results support the hypothesis that pp1 constitutively keeps cyclin d3 in a stable, dephosphorylated state

SIGNOR-142884

O14920

Q04864

1

phosphorylation

up-regulates activity

0.62

We are the first to identify Ser484 and Ser494 as the major sites of in vitro phosphorylation of REL by IKKalpha and IKKbeta.

SIGNOR-279620

Q9P0L9

Q9UQM7

0

phosphorylation

down-regulates activity

0.2

CaM inhibits the function of TRPP3 through promoting CaMK2's phosphorylation towards T591 on TRPP3.

SIGNOR-277812

P68400

Q01082

1

phosphorylation

down-regulates

0.334

We show here that the short c-terminal splice variant of betaii-spectrin (betaiisigma2) is a substrate for phosphorylation. In vitro, protein kinase ck2 phosphorylates ser-2110 and thr-2159 / phosphorylation of ?II?2 C-terminal fragment inhibits its interaction with ?II N-terminal fragment.

SIGNOR-150471

A6NJ46

Q9NS71

1

transcriptional regulation

up-regulates quantity by expression

0.371

In particular, NKX6.3 transcriptional factor was found to bind specifically to the upstream sequences of GKN1, a gastric-specific tumor suppressor, and dramatically increase expression of the latter.

SIGNOR-266096

P49840

P31751

0

phosphorylation

down-regulates

0.557

Activated pi3k/akt pathway results in inhibitory phosphorylation of gsk3

SIGNOR-138179

P49841

Q92585

1

phosphorylation

down-regulates

0.2

We found that gsk3beta inhibits maml1 transcriptional activity by directly targeting the n-terminal domain of maml1

SIGNOR-187896

P30304

P14618

1

dephosphorylation

up-regulates activity

0.487

Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2 dependent beta-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.|Cdc25A dephosphorylates PKM2 at S37, and promotes PKM2-dependent \u03b2-catenin transactivation and c-Myc-upregulated expression of the glycolytic genes GLUT1, PKM2 and LDHA, and of CDC25A; thus, Cdc25A upregulates itself in a positive feedback loop.

SIGNOR-276967

Q38SD2

Q96SN8

1

phosphorylation

up-regulates activity

0.505

Interestingly, LRRK1 in turn phosphorylates CDK5RAP2(Cep215), a human homologue of Drosophila Centrosomin (Cnn), in its gamma-tubulin-binding motif, thus promoting the interaction of CDK5RAP2 with gamma-tubulin. LRRK1 phosphorylation of CDK5RAP2 Ser 140 is necessary for CDK5RAP2-dependent microtubule nucleation.

SIGNOR-275468

P00519

Q06124

1

phosphorylation

up-regulates activity

0.374

Direct phosphorylation of SHP-2 by Abl kinases (Y580) promotes sustained activation of SHP-2 signaling and proliferation, and c-Abl/Abl-Related Gene-dependent activation of tyrosine kinase X further potentiates SHP-2 signaling by phosphorylating SHP-2 on Y63.|Endogenous Abl kinases phosphorylate SHP-2 on Y580 and induce sustained ERK phosphorylation in response to PDGF.

SIGNOR-278217

P31749

O60825

1

phosphorylation

up-regulates activity

0.654

These findings suggest that PKB-dependent binding of 14-3-3s to phospho-Ser483 of cardiac PFK-2 mediates the stimulation of glycolysis by growth factor.

SIGNOR-252555

P53355

Q16623

1

phosphorylation

down-regulates activity

0.339

Syntaxin-1A phosphorylation by DAP kinase or its S188D mutant, which mimics a state of complete phosphorylation, significantly decreases syntaxin binding to Munc18-1, a syntaxin-binding protein that regulates SNARE complex formation and is required for synaptic vesicle docking.

SIGNOR-251083

P60953

Q9NYF5

0

gtpase-activating protein

down-regulates activity

0.452

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-260504

P49841

Q6U7Q0

1

phosphorylation

down-regulates quantity by destabilization

0.2

CK1delta and GSK3beta kinases sequentially phosphorylate ZNF322A at serine-396 and then serine-391. Moreover, the doubly phosphorylated ZNF322A protein creates a destruction motif for the ubiquitin ligase FBXW7alpha leading to ZNF322A protein destruction.

SIGNOR-264891

A7KAX9

Q13480

0

relocalization

up-regulates

0.314

Gc-gap, a rho family gtpase-activating protein that interacts with signaling adapters gab1 and gab2.

SIGNOR-102586

Q12913

P09619

1

dephosphorylation

down-regulates activity

0.582

Primary sequence determinants responsible for site-selective dephosphorylation of the PDGF beta-receptor by the receptor-like protein tyrosine phosphatase DEP-1|DEP-1 dephosphorylation of original and chimeric phospho-peptides spanning the preferred pY1021

SIGNOR-248704

P41743

P15311

1

phosphorylation

up-regulates

0.342

Pkciota phosphorylated ezrin on t567 in vitro, and in sf9 cells that do not activate human ezrin. we conclude that, although other molecular mechanisms contribute to ezrin activation, apically localized phosphorylation by pkciota is essential for the activation and normal distribution of ezrin at the early stages of intestinal epithelial cell differentiation.

SIGNOR-160855

P54646

Q9UQB8

1

phosphorylation

down-regulates

0.2

Using this approach for ppp1r12c, baiap2, and cdc27, we found that mutation of a single serine to alanine (s452, s366, and s379 respectively) resulted in almost a complete loss of ampk phosphorylation in these proteins. Termination of irsp53 function is suggested to occur following cdc42 dissociation, kinase phosphorylation of t340 and t360, and subsequent 14-3-3 binding, which competes for sh3 partners, thus allowing filopodial retraction

SIGNOR-195102

P27361

P00533

1

phosphorylation

down-regulates

0.557

It is likely that the map2 and ert kinases account for the phosphorylation of the egf receptor at thr669 (egf receptor (krel veplt669psgeapnqallr)) observed in cultured cells.Phosphorylation at ser-695 is partial and occurs only if thr-693 is phosphorylated. Phosphorylation at thr-678 and thr-693 by prkd1 inhibits egf-induced mapk8/jnk1 activation.

SIGNOR-20549

P12931

A1X283

1

phosphorylation

up-regulates activity

0.521

C-Src-mediated phosphorylation of NoxA1 and Tks4 induces the reactive oxygen species (ROS)-dependent formation of functional invadopodia in human colon cancer cells|Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.

SIGNOR-264705

P49674

Q9UJU2

1

phosphorylation

down-regulates

0.268

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

SIGNOR-134497

O95140

Q9UKV5

0

polyubiquitination

down-regulates quantity by destabilization

0.3

Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2.

SIGNOR-272887

Q99550

Q6IQ55

0

phosphorylation

down-regulates quantity

0.2

Additionally, in vivo ubiquitin assays showed that expression of either the kinase-dead TTBK2 or the MPP9-S629 and S636-2A mutant significantly decreased the ubiquitination level of MPP9.|Also, the S629A mutant almost abolished the phosphorylation of MPP9 by TTBK2 in the kinase assay in vitro, suggesting that S629 is the main site for MPP9 phosphorylation by TTBK2.

SIGNOR-278998

Q05513

Q16612

1

phosphorylation

down-regulates quantity by destabilization

0.2

Site-directed mutagenesis of S59A retarded P311 degradation and induced glioma cell motility. In contrast, S59D mutation resulted in the rapid degradation of P311 and reduced glioma cell migration.Taken together, our results show that the serine phosphorylation of P311 is dependent on the function of both PKCε and PKCz.

SIGNOR-273831

P78362

P31749

0

phosphorylation

up-regulates

0.465

Here we show that srpk2, a protein kinase specific for the serine/arginine (sr) family of splicing factors, triggers cell cycle progression in neurons and induces apoptosis through regulation of nuclear cyclin d1. Akt phosphorylates srpk2 on thr-492 and promotes its nuclear translocation leading to cyclin d1 up-regulation, cell cycle reentry, and neuronal apoptosis.

SIGNOR-186760

Q03135

O60260

0

ubiquitination

down-regulates quantity

0.2

Parkin induces the degradation of cav-1 through the proteasome dependent pathway.|We also demonstrated that WT parkin ubiquitinates cav-1 for degradation.

SIGNOR-278710

Q13043

Q12778

1

phosphorylation

up-regulates

0.595

Bonni and coworkers demonstrated that mst1 can phosphorylate foxo3 (and subsequently, foxo1) principally ser207 (ser212 in foxo1), a conserved site in the forkhead domain. This phosphorylation interdicts 14-3-3 binding, promotes foxo nuclear residence and transcriptional activity. The other major signaling modules that directly regulate the activity of the foxo factors include the stress-activated jun-n-terminal kinase (jnk), the mammalian ortholog of the ste20-like protein kinase (mst1), and the deacetylase sirt1.

SIGNOR-191847

P78411

Q9NZV8

1

transcriptional regulation

down-regulates quantity by repression

0.487

Irx5 Directly Represses the Kcnd2 Promoter

SIGNOR-266045

Q96LC9

P45983

0

phosphorylation

up-regulates activity

0.689

Activated JNK causes BimL and Bmf phosphorylation in vivo. It is known that UV radiation causes the release of Bim and Bmf from dynein and myosin V motor complexes and that these proteins cause Bax/Bak-dependent apoptosis . The results of this study demonstrate that JNK can engage this apoptotic pathway by phosphorylation of BH3-only proteins, including Bim and Bmf.

SIGNOR-250116

O95292

Q92953

0

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-262123

Q07820

Q9Y577

0

polyubiquitination

down-regulates quantity by destabilization

0.444

Here, we identified Trim17 as a novel E3 ubiquitin-ligase for Mcl-1. Indeed, Trim17 co-immunoprecipitated with Mcl-1. Trim17 ubiquitinated Mcl-1 in vitro. Overexpression of Trim17 decreased the protein level of Mcl-1 in a phosphorylation- and proteasome-dependent manner. Finally, knock down of Trim17 expression reduced both ubiquitination and degradation of Mcl-1 in neurons.

SIGNOR-272032

Q13191

P36888

1

ubiquitination

down-regulates activity

0.326

Functionally, CBL negatively regulated FMS-like tyrosine kinase 3 (FLT3) activity and interacted with human FLT3 via the autophosphorylation sites Y589 and Y599 and colocalized in vivo.

SIGNOR-260106

O15379

P49327

1

deacetylation

up-regulates quantity by stabilization

0.2

Overexpression of HA-HDAC3 decreased the acetylation level of endogenous FASN by 35% in HEK293T cells, while the expression of a catalytic inactive mutant HDAC3Y298H (38) failed to reduce FASN acetylation (Fig. 4C). Conversely, HDAC3 knockdown increased the acetylation level of endogenous FASN by >1.5-fold in HEK293T cells

SIGNOR-267367

Q07912

P31749

1

phosphorylation

up-regulates activity

0.427

Ack1 (also known as ACK or TNK2), which directly phosphorylates AKT at an evolutionarily conserved tyrosine 176 in the kinase domain. Tyr176-phosphorylated AKT localizes to the plasma membrane and promotes Thr308/Ser473-phosphorylation leading to AKT activation.

SIGNOR-252446

P45983

P05412

1

phosphorylation

up-regulates activity

0.907

JNK1 binds to the c-Jun transactivation domain and phosphorylates it on Ser-63 and Ser-73. The effect on AP-1 transcriptional activity results, in part, from enhanced phosphorylation of the c-Jun NH2-terminal activation domain.

SIGNOR-250122

Q9NQU5

P08134

1

phosphorylation

down-regulates activity

0.2

It is possible that Pak6 may directly phosphorylate RhoC to regulate its activity.|Nevertheless, our results clearly show that the kinase activity of Pak6 is required to inhibit RhoC induced cell contraction.

SIGNOR-280059

P00734

P00451

1

cleavage

up-regulates activity

0.755

Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689.

SIGNOR-263640

P05771

Q99418

1

phosphorylation

down-regulates activity

0.307

ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain. Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6]. Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'.

SIGNOR-249024

Q14493

Q16778

1

translation regulation

up-regulates quantity by expression

0.2

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

SIGNOR-265386

Q9UBE8

O43318

0

phosphorylation

up-regulates

0.651

The tak1-nlk-mapk-related pathway antagonizes signalling between beta-catenin and transcription factor tcf.

SIGNOR-96425

Q13153

Q02750

1

phosphorylation

up-regulates activity

0.582

We find that adhesion to fibronectin induces pak1-dependent phosphorylation of mek1 on s298 and that this phosphorylation is necessary for efficient activation of mek1 and subsequent mapk activation.

SIGNOR-236002

P08246

P05546

1

cleavage

down-regulates activity

0.451

Amino acid sequence analysis led to the conclusion that both neutrophil elastase and cathepsin G cleave HC at Ile66, which does not affect HC activity, and at Val439, near the reactive site Leu444, which inactivates HC.

SIGNOR-256510

Q96SB4

P53671

0

phosphorylation

up-regulates activity

0.2

In vitro kinase assays revealed that LIMK2 phosphorylates SRPK1 (Fig. xref ).|LIMK2 promotes the metastatic progression of triple-negative breast cancer by activating SRPK1.

SIGNOR-279625

Q8NFU7

Q96SR6

1

transcriptional regulation

up-regulates quantity by expression

0.2

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

SIGNOR-259095