GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q99466	Q96JK9	2	binding	up-regulates	0.867	Whereas maml1 and maml2 functioned efficiently as coactivators with each of the notch receptors to transactivate a notch target hes1 promoter construct, maml3 functioned more efficiently with icn4 than with other forms of icn.	SIGNOR-94103
Q96JK9	Q99466	2	binding	up-regulates	0.867	Moreover, as determined by using coimmunoprecipitation assays, each maml protein was found to be capable of forming a multiprotein complex with the intracellular domain of each notch receptor (icn1 to -4) and csl in vivo	SIGNOR-94109
P38936	Q00534	2	phosphorylation	down-regulates activity	0.864	Here, we show that p21cip1 is associated with k cyclin both in overexpression models and in primary effusion lymphoma cells and is a substrate of the k cyclin/cdk6 complex, resulting in phosphorylation of p21cip1 on serine 130. This phosphoform of p21cip1 appeared unable to associate with cdk2 in vivo.	SIGNOR-144832
Q00534	P38936	2	binding	down-regulates	0.864	P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage.We Have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases	SIGNOR-30030
O43683	P53350	2	phosphorylation	up-regulates activity	0.864	Note that PLK1 phosphorylates and activates BUB1 to localize it to the kinetochore, phosphorylates and inhibits the negative regulator PKMYTI and interacts with the G1/S kinase Cdc7p to target it to initiation complexes late in G1.	SIGNOR-279251
P53350	O43683	2	binding	up-regulates	0.864	The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609	SIGNOR-147061
P30307	P06493	2	phosphorylation	up-regulates	0.858	Phosphorylation at thr-48, thr-67, ser-122, thr-130, ser-168 and ser-214 occurs at g2 and g2-m transition and is catalyzed by cdk1. Ser-168 phosphorylation levels are lower than those at the other 5 cdk1 sites. Phosphorylation by cdk1 leads to increased activity.	SIGNOR-64960
P30291	P06493	2	phosphorylation	down-regulates	0.858	We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP	SIGNOR-123824
P06493	P30307	2	dephosphorylation	up-regulates	0.858	Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c	SIGNOR-186621
P06493	P30291	2	phosphorylation	down-regulates	0.858	The wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (cdk1), thereby delaying entry into mitosis until appropriate conditions have been met	SIGNOR-139491
Q13315	O60934	2	binding	up-regulates	0.856	Nbs1 can also immobilize atm at the site of the dsb via direct binding of atm to a c-terminal atm interaction motif on nbs1 . the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm	SIGNOR-134508
O60934	Q13315	2	phosphorylation	up-regulates	0.856	In this report, we showed that atm phosphorylates a p95 peptide (ser-343) and a mre11 peptide (ser-264) in vitro, suggesting that atm may regulate the function of p95?Mre11? Rad50 repair complex in response to dna damage.	SIGNOR-73432
Q16828	P27361	2	phosphorylation	down-regulates	0.855	Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3	SIGNOR-132975
P27361	Q16828	2	dephosphorylation	down-regulates	0.855	P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).	SIGNOR-103149
Q07817	Q92934	2	binding	down-regulates activity	0.848	Bad binds more strongly to Bcl-x, than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-x,, but not that of Bcl-2. When Bad dimerized with Bcl-x,, Bax was displaced and apoptosis was restored.	SIGNOR-249617
Q92934	Q07817	2	binding	up-regulates activity	0.848	Bad dimerizes with bcl-xl at the mitochondrial membrane where it exert its killing effects. Phosphorylation of bad promotes its binding to 14-3-3 protein, which may sequester bad from bcl-xl, thus promoting cell cells survival.	SIGNOR-81125
Q99708	P38398	2	ubiquitination	up-regulates	0.842	In conclusion, our data show that ctip is a physiological substrate of the brca1 e3 ligase. Brca1 recruits ctip through its c-terminal brct domains and promotes ctip ubiquitination through its n-terminal ring domain. The ubiquitinated ctip is not targeted for degradation. Instead, ubiquitinated ctip binds to chromatin following dna damage and is likely to be involved in dna damage checkpoint control.	SIGNOR-147711
P38398	Q99708	2	relocalization	up-regulates activity	0.842	DNA damage activates ATM and CHK2 kinases, which mediate phosphorylation of CtIP and BRCA1. Phosphorylated CtIP associates with BRCA1 and with the MRN complex leading to the recruitment of the BRCC complex at the site of DNA damage where HR is initiated.	SIGNOR-263203
P30304	P06493	2	phosphorylation	up-regulates	0.842	Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.	SIGNOR-95260
P06493	P30304	2	dephosphorylation	up-regulates activity	0.842	Phosphatase activity of Cdc25A is critical for its activating capacity (data not shown). In this context, it should also be mentioned that Cdc25A is able to activate cyclin B-Cdk1 in vitro	SIGNOR-248480
Q9UER7	Q99683	2	phosphorylation	up-regulates	0.841	Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha.	SIGNOR-188321
Q99683	Q9UER7	2	binding	up-regulates	0.841	Daxx was found to activate the jnk kinase kinase ask1, and overexpression of a kinase-deficient ask1 mutant inhibited fas- and daxx-induced apoptosis and jnk activation.	SIGNOR-60164
P43403	P15498	2	binding	up-regulates activity	0.838	In summary, we demonstrate here that Y315 in ZAP-70 is required to interact with the Vav SH2 domain, and is critical for ZAP-70–mediated gene activation.	SIGNOR-274150
P15498	P43403	2	phosphorylation	up-regulates activity	0.838	These results suggest that CBAP may serve as an adaptor or scaffold in the integrin \u03b21/CBAP/ZAP70-containing complex that, upon chemokine treatment, would allow Vav1 or ZAP70 (or both) to adopt an optimal conformation(s) for ZAP70 to phosphorylate Vav1.\|Together, these results suggested that CBAP is an important component in ZAP70 dependent activation of the Vav1 and Rac1 signaling axis.	SIGNOR-278390
Q13188	Q9H4B6	2	binding	up-regulates	0.834	Mst is activated by binding of salvador (sav1, sav in drosophila), which is, in turn, also phosphorylated by mst.	SIGNOR-169829
Q9H4B6	Q13188	2	phosphorylation	up-regulates	0.834	In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav	SIGNOR-230716
Q9HCE7	O43541	2	binding	up-regulates activity	0.831	Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase.	SIGNOR-272786
O43541	Q9HCE7	2	relocalization	down-regulates activity	0.831	Smurf1, with its WW domain, specifically binds to the PY motif of Smad6 and transports Smad6 into the cytoplasm.	SIGNOR-105931
P24941	P30304	2	dephosphorylation	up-regulates activity	0.83	The phosphatase activity of Cdc25A is necessary for Cdk2 activation, most likely due to dephosphorylation on Tyr-15 and Thr-14 of Cdk2.	SIGNOR-248481
Q8ND76	O94921	2	phosphorylation	down-regulates quantity by destabilization	0.83	Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation\|Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex	SIGNOR-273007
P30304	P24941	2	phosphorylation	down-regulates	0.83	We show here that dna-responsive checkpoints activate pp2a/b56delta phosphatase complexes to dephosphorylate cdc25 at a site distinct from ser287 (t138), the phosphorylation of which is required for 14-3-3 release.	SIGNOR-150839
O94921	Q8ND76	2	binding	up-regulates	0.83	L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.	SIGNOR-162920
P06493	P30305	2	dephosphorylation	up-regulates activity	0.829	CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G 2 /M transition ( xref ).\|CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G2/M transition ( ).	SIGNOR-276969
Q8NFZ4	Q9P2S2	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265454
P30305	P06493	2	phosphorylation	up-regulates	0.829	Ser(321) is phosphorylated in mitosis by cdk1. The mitotic phosphorylation of ser(321) acts to maintain full activation of cdc25b by disrupting 14-3-3 binding to ser(323) and enhancing the dephosphorylation of ser(323) to block 14-3-3 binding to this site.	SIGNOR-167641
Q8NFZ4	P58401	2	binding	up-regulates activity	0.829	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265455
P58401	Q8NFZ4	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264161
Q9P2S2	Q8NFZ4	2	binding	up-regulates activity	0.829	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264156
Q9Y6K9	O95999	2	binding	up-regulates	0.827	Here, we show that bcl10 undergoes k63-linked polyubiquitination in response to t cell activation and subsequently binds nemo, the regulatory subunit of ikk.	SIGNOR-160967
O95999	Q9Y6K9	2	ubiquitination	up-regulates activity	0.827	Here we show that Bcl10 targets NEMO for lysine-63-linked ubiquitination. Notably, a mutant form of NEMO that cannot be ubiquitinated inhibited Bcl10-induced NF-κB activation.	SIGNOR-274149
Q8NFZ4	Q9HDB5	2	binding	up-regulates activity	0.825	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265456
Q9Y4C0	Q8NFZ4	2	binding	up-regulates activity	0.825	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264166
P58400	Q8NFZ4	2	binding	up-regulates activity	0.825	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264151
Q8NFZ4	P58400	2	binding	up-regulates activity	0.825	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265453
Q8NFZ4	Q9ULB1	2	binding	up-regulates activity	0.825	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites.	SIGNOR-265452
Q9ULB1	Q8NFZ4	2	binding	up-regulates activity	0.825	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264146
Q9HDB5	Q8NFZ4	2	binding	up-regulates activity	0.825	Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.\|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)	SIGNOR-264171
Q8NFZ4	Q9Y4C0	2	binding	up-regulates activity	0.825	The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites	SIGNOR-265457
Q15256	P28482	2	phosphorylation	up-regulates activity	0.824	Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.	SIGNOR-249438
P28482	Q15256	2	dephosphorylation	down-regulates activity	0.824	Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.\|PTP-SL dephosphorylates the regulatory phosphotyrosine on the active loop of ERK1/2. Tyrosine dephosphorylation of ERK1/2 causes the inactivation of ERK1/2 and its retention in the cytoplasm	SIGNOR-248840
Q16539	Q15750	2	binding	up-regulates activity	0.823	In contrast to MKK3-induced p38 kinase downstream effects, TAB-1-induced p38 kinase activation does not induce expression of pro-inflammatory genes, cardiac marker gene expression, or changes in cellular morphology. Rather, TAB-1 binds to p38 and prevents p38 nuclear localization.	SIGNOR-143576
Q15750	Q16539	2	phosphorylation	down-regulates activity	0.823	Tab1, a subunit of the kinase tak1, was phosphorylated by sapk2a/p38alpha at ser423, thr431 and ser438 in vitro. the results presented here also show that sapk2a/p38? Suppresses the activity of tak1 in cells, because the activation of tak1 by proinflammatory cytokines and lps is enhanced if cells are first pre?incubated With sb 203580 or in cells that do not express sapk2a/p38?.	SIGNOR-118922
P11021	P18850	2	transcriptional regulation	up-regulates quantity by expression	0.821	Accordingly, N-terminal fragments of each ATF6 isoform (N-ATF6α and N-ATF6β) were overexpressed in HeLa cells and the effects on GRP78 induction were assessed. When expressed at similar levels, N-ATF6α conferred ∼200-fold greater GRP78 promoter activation than N-ATF6β.	SIGNOR-261565
P18850	P11021	2	binding	down-regulates activity	0.821	Similar to PERK and IRE1, ATF6 is activated by ER stress-induced dissociation from GRP78	SIGNOR-260179
Q01094	Q14186	2	binding	up-regulates activity	0.815	DP-1 is a heterodimerization partner for members of the E2F family of transcription factors; E2F/DP-1 regulates the expression of various cellular promoters, particularly gene products that are involved in the cell cycle.	SIGNOR-253865
Q14186	Q01094	2	binding	up-regulates activity	0.815	The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family.In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3.	SIGNOR-240547
P28482	P35236	2	dephosphorylation	down-regulates activity	0.812	HePTP efficiently dephosphorylated active ERK2 on the tyrosine residue in the activation loop in vitro. Together, these data identify ERK2 as a specific and direct target of HePTP and are consistent with a model in which HePTP negatively regulates ERK2 activity as part of a feedback mechanism	SIGNOR-248484
P35236	P28482	2	phosphorylation	up-regulates activity	0.812	First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185.\|	SIGNOR-249436
Q13651	P23458	2	phosphorylation	up-regulates activity	0.809	Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3).	SIGNOR-251338
P23458	Q13651	2	binding	up-regulates activity	0.809	Specifically, il-10 effects the activation of jak1 (associated with the il-10 receptor alpha Chain) and tyk2 (associated with the il-10 receptor beta Chain) and induces the activation of stat1, stat3, and, in some cells, stat5.	SIGNOR-68010
Q16539	P28562	2	dephosphorylation	down-regulates activity	0.805	The activity of MAPKs can be also regulated by a family of DUSPs (dual-specificity phosphatases)/MKPs (MAPK phosphatases), which dephosphorylate both phosphotyrosine and phosphothreonine residues MKPs 1, 4, 5 and 7 can dephosphorylate p38_ and p38_ in addition to JNK MAPKs. Importantly, some MKPs are transcriptionally up-regulated by stimuli that activate MAPK signalling, and are thought to play an important role limiting the extent of MAPK activation	SIGNOR-166571
P28482	P28562	2	dephosphorylation	down-regulates activity	0.805	We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively	SIGNOR-248465
P28562	P28482	2	phosphorylation	down-regulates	0.805	The dual-specificity mapk phosphatase mkp-1/cl100/dusp1 is an inducible nuclear protein controlled by p44/42 mapk (erk1/2) in a negative feedback mechanism to inhibit kinase activity. Here, we report on the molecular basis for a novel positive feedback mechanism to sustain erk activation by triggering mkp-1 proteolysis. Active erk2 docking to the def motif (fxfp, residues 339-342) of n-terminally truncated mkp-1 in vitro initiated phosphorylation at the ser(296)/ser(323) domain	SIGNOR-141593
P28562	Q16539	2	binding	up-regulates activity	0.805	Here we have shown that mkp-1 associates directly with p38 map kinase both in vivo and in vitro, and that this interaction enhances the catalytic activity of mkp-1. The point mutation asp-316-->asn in the c-terminus of p38, analogous to the erk2 (extracellular-signal-regulated kinase 2) sevenmaker mutation, dramatically decreases its binding to mkp-1 and substantially compromises its stimulatory effect on the catalytic activity of this phosphatase.	SIGNOR-83752
Q8TEP8	O14965	2	phosphorylation	up-regulates activity	0.796	Thus, following their sequential activation in Cep192 complexes, both AurA and Plx1 phosphorylate Cep192.\|We found that Cep192 1\u20131000 -wt promoted AurA and Plx1 activation and itself underwent phosphorylation irrespective of whether it was bound to the endogenous or recombinant Plx1 (i.e. whether Plx1 was docked onto T46 or not) (lanes 6 and 8).	SIGNOR-279797
O14965	Q8TEP8	2	binding	up-regulates activity	0.796	These findings demonstrated that Cep192 mediates the AurA-Plk1 interaction and that the formation of the Cep192-AurA-Plk1 complex could be important for activating AurA and Plk1.	SIGNOR-266406
O14757	Q9HAW4	2	binding	up-regulates	0.794	Binding of claspin to xchk1 is highly elevated in the presence of dna templates that trigger a checkpoint arrest of the cell cycle in xenopus egg extracts	SIGNOR-84474
Q9HAW4	O14757	2	phosphorylation	up-regulates	0.794	We found that thr-916 on claspin is phosphorylated by chk1, suggesting that chk1 regulates claspin during checkpoint response.	SIGNOR-149411
Q06124	O60674	2	phosphorylation	up-regulates activity	0.793	Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2	SIGNOR-236266
O60674	Q06124	2	dephosphorylation	up-regulates quantity by stabilization	0.793	We report that SHP-2 dephosphorylates tyrosine (Tyr-1007) of Jak2 kinase, a critical recruitment site for the ubiquitin ligase-associated inhibitory protein suppressor of cytokine signaling-1 (SOCS-1), thereby contributing to Jak2 stability. Inactivation of SHP-2 function by blocking receptor/SHP-2 association or by using a catalytically inactive mutant of SHP-2 led to a marked increase in Jak2 ubiquitination/degradation, Jak2 phosphorylation on Tyr-1007, and Jak2/SOCS-1 association	SIGNOR-248665
Q9NR28	Q13489	2	ubiquitination	down-regulates quantity by destabilization	0.792	Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate-dependent E3 activity of cIAPs is mediated by their RING domains and is dependent on the specific interactions between cIAPs and Smac.	SIGNOR-271391
Q13489	Q9NR28	2	binding	down-regulates quantity	0.792	Smac/diablo selectively causes the rapid degradation of c-iap1 and c-iap2 in hela cells. Smac binding to c-iap via its n-terminal iap-binding motif is the prerequisite for this effect	SIGNOR-121886
P02647	O95477	2	binding	up-regulates activity	0.79	The stimulation of cellular cholesterol and phospholipid efflux by apolipoprotein A-I is mediated by the activity of the ATP-binding cassette transporter A1 (ABCA1). ABCA1 forms a high affinity complex with apoA-I by binding amphipathic helices within the apolipoprotein. VFVNFA sequence is required for ABCA1 to form a complex with apoA-I and to transfer cholesterol to the apolipoprotein.	SIGNOR-252100
O95477	P02647	2	binding	up-regulates quantity by stabilization	0.79	ApoA-I stabilization of ABCA1 is mediated by reduced PEST sequence phosphorylation, which in turn leads to decreased calpain proteolysis of ABCA1.	SIGNOR-252101
Q96CV9	Q9UHD2	2	phosphorylation	up-regulates activity	0.789	Given that TBK1 can phosphorylate OPTN on S177, S473 and S513 in response to mitochondrial depolarization, we explored the function of these events in vivo.\|Phosphorylation of OPTN on S473 and S513 promotes TBK1 activation and recruitment of OPTN to depolarized mitochondria.	SIGNOR-278170
Q9UHD2	Q96CV9	2	binding	up-regulates activity	0.789	Using biochemical experiments we showed that optineurin interacts with the protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, a mutation in optineurin that prevents the interaction with the small protein modifier ubiquitin (D474N) ablated the negative regulatory function of optineurin.	SIGNOR-262276
P18031	P06213	2	phosphorylation	up-regulates activity	0.788	Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex\| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B	SIGNOR-249370
P06213	P18031	2	dephosphorylation	down-regulates activity	0.788	Ptp1b is a protein tyrosine phosphatase that negatively regulates insulin sensitivity by dephosphorylating the insulin receptor.	SIGNOR-235499
Q6PGQ7	P53350	2	phosphorylation	down-regulates	0.788	Following cdk1-dependent recruitment, plk1 triggers hbora destruction by phosphorylating a recognition site for scf(beta-trcp).	SIGNOR-178154
P53350	Q6PGQ7	2	phosphorylation	up-regulates	0.788	Bora/aurora-a-dependent phosphorylation is a prerequisite for plk1 to promote mitotic entry after a checkpoint-dependent arrest.	SIGNOR-179425
Q6VVB1	O95278	2	binding	up-regulates activity	0.787	Here, we provide evidence indicating that the formation of the laforin–malin complex is positively regulated by AMPK. We show that laforin, but not malin, can interact physically with the catalytic subunit of AMPK and that purified AMPK phosphorylates GST::laforin in vitro.	SIGNOR-271729
O95278	Q6VVB1	2	polyubiquitination	down-regulates quantity by destabilization	0.787	Here, we demonstrate that malin is a single subunit E3 ubiquitin (Ub) ligase and that its RING domain is necessary and sufficient to mediate ubiquitination. Additionally, malin interacts with and polyubiquitinates laforin, leading to its degradation.	SIGNOR-271547
P28562	P27361	2	phosphorylation	up-regulates	0.786	Mkp-1 was a target in vivo and in vitro for p42(mapk) or p44(mapk), which phosphorylates mkp-1 on two carboxyl-terminal serine residues, serine 359 and serine 364. This phosphorylation did not modify mkp-1's intrinsic ability to dephosphorylate p44(mapk) but led to stabilization of the protein.	SIGNOR-73633
P27361	P28562	2	dephosphorylation	down-regulates activity	0.786	We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively	SIGNOR-248462
Q9HAT8	P51617	2	phosphorylation	up-regulates activity	0.781	The phosphorylation of Pellino2 by activated IRAK1 and IRAK4 could trigger and modulate the translocation of IRAKs from complex I to complex II.	SIGNOR-278947
P51617	Q9HAT8	2	ubiquitination	up-regulates	0.781	These studies suggest that pellino isoforms may be the e3 ubiquitin ligases that mediate the il-1-stimulated formation of k63-pub-irak1 in cells, which may contribute to the activation of ikkbeta and the transcription factor nf-kappab, as well as other pathways dependent on irak1/4.	SIGNOR-159058
Q9HAU4	Q15796	2	binding	up-regulates activity	0.778	We show that in the presence of TGF-beta signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases.Thus, stimulation by TGF-beta can induce the assembly of a Smad2-Smurf2 ubiquitin ligase complex that functions to target substrates for degradation.	SIGNOR-108490
Q15796	Q9HAU4	2	ubiquitination	down-regulates activity	0.778	The ability of smurf2 to promote smad2 destruction required the hect catalytic activity of smurf2 and depended on the proteasome-dependent pathway.	SIGNOR-236133
P49841	Q92837	2	binding	up-regulates	0.776	The frat family consists of three members: frat-1, -2, and -3. It has been shown that different sites of frat-1 interact with gsk-3 and dvl-1 and that wnt-1 disintegrates the complex formation of frat-1, dvl-1, and axin, resulting in the activation of the wnt signaling pathway	SIGNOR-58219
Q92837	P49841	2	phosphorylation	down-regulates activity	0.776	Protein kinase A (PKA) was found to phosphorylate Ser188 in vitro as well as in intact cells. Importantly, activation of endogenous cAMP-coupled beta-adrenergic receptors with norepinephrine stimulated the phosphorylation of FRAT1 at Ser188. GSK-3 was also able to phosphorylate FRAT1 at Ser188 and other residues in vitro or when overexpressed in intact cells. Phosphorylation of Ser188 by PKA inhibited the ability of FRAT1 to activate beta-catenin-dependent transcription.	SIGNOR-276057
P48357	O60674	2	phosphorylation	up-regulates activity	0.774	LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2.	SIGNOR-263494
O60674	P48357	2	binding	up-regulates activity	0.774	Janus kinase 2 (JAK2) is associated with LEPRb and autophosphorylates in response to leptin. JAK2 also phosphorylates LEPRb, STAT3, and multiple other downstream molecules.	SIGNOR-263491
P15391	P07948	2	phosphorylation	up-regulates	0.772	Experiments with purified proteins demonstrated that cd19-y513 was lyn's initial phosphorylation and binding site. This led to processive phosphorylation of cd19-y482, which recruited a second lyn molecule, allowing for transphosphorylation and amplification of lyn activation.	SIGNOR-80290
P07948	P15391	2	binding	up-regulates activity	0.772	CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.	SIGNOR-242894
P45984	Q9UQF2	2	binding	down-regulates	0.769	These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins.	SIGNOR-70854
Q9UQF2	P45984	2	phosphorylation	up-regulates activity	0.769	Recruitment of jnk to jip1 and jnk-dependent jip1 phosphorylation regulates jnk module dynamics and activation it was observed that phosphorylation by jnk of jip1 on thr-103 and not other phosphorylated jip1 residues is necessary for the regulation of dlk association with jip1, dlk activation, and subsequent module activation.	SIGNOR-101201
Q96FA3	P51617	2	phosphorylation	up-regulates activity	0.767	In this article we demonstrate that pellino 1 is phosphorylated at multiple sites by irak1 or irak4 in vitro. The key residues involved in activation are located between residues 76 and 86 (ser-76, ser-78, thr-80, ser-82, and thr-86) and at thr-288 and ser-293, just n-terminal to the ring-like domain that carries the e3 ligase activity. Unusually, we found that the phosphorylation of ser-76 or thr-288 or ser-293 alone was sufficient for maximal activation	SIGNOR-96747
P51617	Q96FA3	2	ubiquitination	up-regulates quantity by expression	0.767	These results were consistent with the observations made in vitro, namely that pellino isoforms are activated by irak1-catalysed phosphorylation and that, once activated, can ubiquitinate irak1 in cells.	SIGNOR-159055
P00533	P18031	2	dephosphorylation	down-regulates activity	0.76	We have shown previously that amino acid residues flanking the phosphotyrosine are important for efficient PTP1 catalysis (Table 1 and Refs. 9, 10, and 17). For example, the kcat/Km value for the undecapeptide, EGFR988-989 (epidermal growth factor autophosphorylation site Tyr992, residues 988-998) (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly) is 3220-fold higher than that of phosphotyrosine (Table 1). We further demonstrated that a minimum of six amino acid residues are required for the most efficient PTP1 binding and catalysis.	SIGNOR-248407
P18031	P00533	2	phosphorylation	up-regulates	0.76	After binding to egfr, ptp1b becomes tyrosine-phosphorylated at tyr-66 phosphorylation of ptp1b by egfr enhances its catalytic activity	SIGNOR-52950

Q99466

Q96JK9

2

binding

up-regulates

0.867

Whereas maml1 and maml2 functioned efficiently as coactivators with each of the notch receptors to transactivate a notch target hes1 promoter construct, maml3 functioned more efficiently with icn4 than with other forms of icn.

SIGNOR-94103

Q96JK9

Q99466

2

binding

up-regulates

0.867

Moreover, as determined by using coimmunoprecipitation assays, each maml protein was found to be capable of forming a multiprotein complex with the intracellular domain of each notch receptor (icn1 to -4) and csl in vivo

SIGNOR-94109

P38936

Q00534

2

phosphorylation

down-regulates activity

0.864

Here, we show that p21cip1 is associated with k cyclin both in overexpression models and in primary effusion lymphoma cells and is a substrate of the k cyclin/cdk6 complex, resulting in phosphorylation of p21cip1 on serine 130. This phosphoform of p21cip1 appeared unable to associate with cdk2 in vivo.

SIGNOR-144832

Q00534

P38936

2

binding

down-regulates

0.864

P21cip1 is a cyclin-dependent kinase (cdk) inhibitor that is transcriptionally activated by p53 in response to dna damage.We Have explored the interaction of p21 with the currently known cdks. p21 effectively inhibits cdk2, cdk3, cdk4, and cdk6 kinases

SIGNOR-30030

O43683

P53350

2

phosphorylation

up-regulates activity

0.864

Note that PLK1 phosphorylates and activates BUB1 to localize it to the kinetochore, phosphorylates and inhibits the negative regulator PKMYTI and interacts with the G1/S kinase Cdc7p to target it to initiation complexes late in G1.

SIGNOR-279251

P53350

O43683

2

binding

up-regulates

0.864

The plk1-bub1 interaction requires the polo-box domain (pbd) of plk1 and is enhanced by cyclin-dependent kinase 1 (cdk1)-mediated phosphorylation of bub1 at t609

SIGNOR-147061

P30307

P06493

2

phosphorylation

up-regulates

0.858

Phosphorylation at thr-48, thr-67, ser-122, thr-130, ser-168 and ser-214 occurs at g2 and g2-m transition and is catalyzed by cdk1. Ser-168 phosphorylation levels are lower than those at the other 5 cdk1 sites. Phosphorylation by cdk1 leads to increased activity.

SIGNOR-64960

P30291

P06493

2

phosphorylation

down-regulates

0.858

We have found also that the major M-phase kinases polo-like kinase 1 (Plk1) and Cdc2 are responsible for the phosphorylation of S53 and S123, respectively, and that in each case phosphorylation generates an unconventional phospho-degron (signal for degradation) that can be recognized by beta-TrCP

SIGNOR-123824

P06493

P30307

2

dephosphorylation

up-regulates

0.858

Cdk1/cdc2 activation involves tyr15/thr14 dephosphorylation by cdc25c

SIGNOR-186621

P06493

P30291

2

phosphorylation

down-regulates

0.858

The wee1 kinase phosphorylates and inhibits cyclin-dependent kinase 1 (cdk1), thereby delaying entry into mitosis until appropriate conditions have been met

SIGNOR-139491

Q13315

O60934

2

binding

up-regulates

0.856

Nbs1 can also immobilize atm at the site of the dsb via direct binding of atm to a c-terminal atm interaction motif on nbs1 . the mre11/rad50/nbs1 (mrn) complex maintains genomic stability by bridging dna ends and initiating dna damage signaling through activation of the atm

SIGNOR-134508

O60934

Q13315

2

phosphorylation

up-regulates

0.856

In this report, we showed that atm phosphorylates a p95 peptide (ser-343) and a mre11 peptide (ser-264) in vitro, suggesting that atm may regulate the function of p95?Mre11? Rad50 repair complex in response to dna damage.

SIGNOR-73432

Q16828

P27361

2

phosphorylation

down-regulates

0.855

Phosphorylation of serines 159 and 197 by erk1/2 enhances proteasomal degradation of mkp-3

SIGNOR-132975

P27361

Q16828

2

dephosphorylation

down-regulates

0.855

P-erk1/2 proteins were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2a (pp1/2a) and mapk phosphatase 3 (mkp3).

SIGNOR-103149

Q07817

Q92934

2

binding

down-regulates activity

0.848

Bad binds more strongly to Bcl-x, than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-x,, but not that of Bcl-2. When Bad dimerized with Bcl-x,, Bax was displaced and apoptosis was restored.

SIGNOR-249617

Q92934

Q07817

2

binding

up-regulates activity

0.848

Bad dimerizes with bcl-xl at the mitochondrial membrane where it exert its killing effects. Phosphorylation of bad promotes its binding to 14-3-3 protein, which may sequester bad from bcl-xl, thus promoting cell cells survival.

SIGNOR-81125

Q99708

P38398

2

ubiquitination

up-regulates

0.842

In conclusion, our data show that ctip is a physiological substrate of the brca1 e3 ligase. Brca1 recruits ctip through its c-terminal brct domains and promotes ctip ubiquitination through its n-terminal ring domain. The ubiquitinated ctip is not targeted for degradation. Instead, ubiquitinated ctip binds to chromatin following dna damage and is likely to be involved in dna damage checkpoint control.

SIGNOR-147711

P38398

Q99708

2

relocalization

up-regulates activity

0.842

DNA damage activates ATM and CHK2 kinases, which mediate phosphorylation of CtIP and BRCA1. Phosphorylated CtIP associates with BRCA1 and with the MRN complex leading to the recruitment of the BRCC complex at the site of DNA damage where HR is initiated.

SIGNOR-263203

P30304

P06493

2

phosphorylation

up-regulates

0.842

Mitotic stabilization of cdc25a reflects its phosphorylation on ser17 and ser115 by cyclin b-cdk1, modifications required to uncouple cdc25a from its ubiquitin-proteasome-mediated turnover.

SIGNOR-95260

P06493

P30304

2

dephosphorylation

up-regulates activity

0.842

Phosphatase activity of Cdc25A is critical for its activating capacity (data not shown). In this context, it should also be mentioned that Cdc25A is able to activate cyclin B-Cdk1 in vitro

SIGNOR-248480

Q9UER7

Q99683

2

phosphorylation

up-regulates

0.841

Our data demonstrated that ask1 controls the cytoplasmic localization of daxx (fig.1). our results indicate that daxx not only activates ask1 but also is a downstream target of ask1 and that accumulated daxx further activates ask1. Thus, the daxx-ask1 positive feedback loop amplifying jnk/p38 signaling plays an important role in the cell-killing effects of stressors, such as tnfalpha.

SIGNOR-188321

Q99683

Q9UER7

2

binding

up-regulates

0.841

Daxx was found to activate the jnk kinase kinase ask1, and overexpression of a kinase-deficient ask1 mutant inhibited fas- and daxx-induced apoptosis and jnk activation.

SIGNOR-60164

P43403

P15498

2

binding

up-regulates activity

0.838

In summary, we demonstrate here that Y315 in ZAP-70 is required to interact with the Vav SH2 domain, and is critical for ZAP-70–mediated gene activation.

SIGNOR-274150

P15498

P43403

2

phosphorylation

up-regulates activity

0.838

These results suggest that CBAP may serve as an adaptor or scaffold in the integrin \u03b21/CBAP/ZAP70-containing complex that, upon chemokine treatment, would allow Vav1 or ZAP70 (or both) to adopt an optimal conformation(s) for ZAP70 to phosphorylate Vav1.|Together, these results suggested that CBAP is an important component in ZAP70 dependent activation of the Vav1 and Rac1 signaling axis.

SIGNOR-278390

Q13188

Q9H4B6

2

binding

up-regulates

0.834

Mst is activated by binding of salvador (sav1, sav in drosophila), which is, in turn, also phosphorylated by mst.

SIGNOR-169829

Q9H4B6

Q13188

2

phosphorylation

up-regulates

0.834

In vitro phosphorylation experiments indicate that the phosphorylation of Sav by Mst is direct. The stabilizing effect of Mst was much greater on N-terminally truncated hSav mutants, as long as they retained the ability to bind Mst. Mst mutants that lacked the C-terminal coiled-coil domain and were unable to bind to hSav, also failed to stabilize or phosphorylate hSav

SIGNOR-230716

Q9HCE7

O43541

2

binding

up-regulates activity

0.831

Smad6 mediates Tbx6 ubiquitination and proteasomal degradation. Tbx6 forms a ternary complex with Smad6 and Smurf1. Here, we report that Tbx6 interacts directly with Smad6, an inhibitory Smad that antagonizes the BMP signal. This interaction is mediated through the Mad homology 2 (MH2) domain of Smad6 and residues 90-180 of Tbx6. We demonstrate that Smad6 facilitates the degradation of Tbx6 protein through recruitment of Smurf1, a ubiquitin E3 ligase.

SIGNOR-272786

O43541

Q9HCE7

2

relocalization

down-regulates activity

0.831

Smurf1, with its WW domain, specifically binds to the PY motif of Smad6 and transports Smad6 into the cytoplasm.

SIGNOR-105931

P24941

P30304

2

dephosphorylation

up-regulates activity

0.83

The phosphatase activity of Cdc25A is necessary for Cdk2 activation, most likely due to dephosphorylation on Tyr-15 and Thr-14 of Cdk2.

SIGNOR-248481

Q8ND76

O94921

2

phosphorylation

down-regulates quantity by destabilization

0.83

Phosphorylation of cyclin Y by CDK14 induces its ubiquitination and degradation|Phosphorylation of CCNY at Serines 71 and 73 creates a putative phospho-degron that controls its association with an SCF complex

SIGNOR-273007

P30304

P24941

2

phosphorylation

down-regulates

0.83

We show here that dna-responsive checkpoints activate pp2a/b56delta phosphatase complexes to dephosphorylate cdc25 at a site distinct from ser287 (t138), the phosphorylation of which is required for 14-3-3 release.

SIGNOR-150839

O94921

Q8ND76

2

binding

up-regulates

0.83

L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6.

SIGNOR-162920

P06493

P30305

2

dephosphorylation

up-regulates activity

0.829

CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G 2 /M transition ( xref ).|CDC25B facilitates dephosphorylation of the key cell cycle regulator CDC2 (also called CDK1) at Tyr15 or Thr14, thereby initiating the G2/M transition ( ).

SIGNOR-276969

Q8NFZ4

Q9P2S2

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265454

P30305

P06493

2

phosphorylation

up-regulates

0.829

Ser(321) is phosphorylated in mitosis by cdk1. The mitotic phosphorylation of ser(321) acts to maintain full activation of cdc25b by disrupting 14-3-3 binding to ser(323) and enhancing the dephosphorylation of ser(323) to block 14-3-3 binding to this site.

SIGNOR-167641

Q8NFZ4

P58401

2

binding

up-regulates activity

0.829

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265455

P58401

Q8NFZ4

2

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264161

Q9P2S2

Q8NFZ4

2

binding

up-regulates activity

0.829

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264156

Q9Y6K9

O95999

2

binding

up-regulates

0.827

Here, we show that bcl10 undergoes k63-linked polyubiquitination in response to t cell activation and subsequently binds nemo, the regulatory subunit of ikk.

SIGNOR-160967

O95999

Q9Y6K9

2

ubiquitination

up-regulates activity

0.827

Here we show that Bcl10 targets NEMO for lysine-63-linked ubiquitination. Notably, a mutant form of NEMO that cannot be ubiquitinated inhibited Bcl10-induced NF-κB activation.

SIGNOR-274149

Q8NFZ4

Q9HDB5

2

binding

up-regulates activity

0.825

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265456

Q9Y4C0

Q8NFZ4

2

binding

up-regulates activity

0.825

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264166

P58400

Q8NFZ4

2

binding

up-regulates activity

0.825

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264151

Q8NFZ4

P58400

2

binding

up-regulates activity

0.825

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265453

Q8NFZ4

Q9ULB1

2

binding

up-regulates activity

0.825

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites.

SIGNOR-265452

Q9ULB1

Q8NFZ4

2

binding

up-regulates activity

0.825

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264146

Q9HDB5

Q8NFZ4

2

binding

up-regulates activity

0.825

Pre- and postsynaptic plasma membranes are always precisely aligned, and are separated by a synaptic cleft of ~20 nm. The cleft contains an undefined proteinaceous material in the middle, and is presumably bridged by synaptic cell-adhesion molecules such as Nrxns and Nlgns that align the pre- and postsynaptic elements and mediate trans-synaptic signaling.|Nlgns bind to both alpha- and beta-Nrxns with nanomolar affinities; binding involves the sixth LNS-domain of alpha-Nrxns which corresponds to the only LNS-domain of beta-Nrxns52. The binding affinities differ characteristically between various pairs of Nlgns and Nrxns, and are controlled by alternative splicing of both Nrxns and Nlgns (Figure 1c)

SIGNOR-264171

Q8NFZ4

Q9Y4C0

2

binding

up-regulates activity

0.825

The neurexin–NL2 interaction is sufficient to induce GABAergic differentiation and clustering of GABAARs at postsynaptic sites

SIGNOR-265457

Q15256

P28482

2

phosphorylation

up-regulates activity

0.824

Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.

SIGNOR-249438

P28482

Q15256

2

dephosphorylation

down-regulates activity

0.824

Specifically, the complex formation between PTP-SL and ERK2 involves an unusual interaction leading to the phosphorylation of PTP-SL by ERK2 at Thr253 and the inactivating dephosphorylation of ERK2 by PTP-SL.|PTP-SL dephosphorylates the regulatory phosphotyrosine on the active loop of ERK1/2. Tyrosine dephosphorylation of ERK1/2 causes the inactivation of ERK1/2 and its retention in the cytoplasm

SIGNOR-248840

Q16539

Q15750

2

binding

up-regulates activity

0.823

In contrast to MKK3-induced p38 kinase downstream effects, TAB-1-induced p38 kinase activation does not induce expression of pro-inflammatory genes, cardiac marker gene expression, or changes in cellular morphology. Rather, TAB-1 binds to p38 and prevents p38 nuclear localization.

SIGNOR-143576

Q15750

Q16539

2

phosphorylation

down-regulates activity

0.823

Tab1, a subunit of the kinase tak1, was phosphorylated by sapk2a/p38alpha at ser423, thr431 and ser438 in vitro. the results presented here also show that sapk2a/p38? Suppresses the activity of tak1 in cells, because the activation of tak1 by proinflammatory cytokines and lps is enhanced if cells are first pre?incubated With sb 203580 or in cells that do not express sapk2a/p38?.

SIGNOR-118922

P11021

P18850

2

transcriptional regulation

up-regulates quantity by expression

0.821

Accordingly, N-terminal fragments of each ATF6 isoform (N-ATF6α and N-ATF6β) were overexpressed in HeLa cells and the effects on GRP78 induction were assessed. When expressed at similar levels, N-ATF6α conferred ∼200-fold greater GRP78 promoter activation than N-ATF6β.

SIGNOR-261565

P18850

P11021

2

binding

down-regulates activity

0.821

Similar to PERK and IRE1, ATF6 is activated by ER stress-induced dissociation from GRP78

SIGNOR-260179

Q01094

Q14186

2

binding

up-regulates activity

0.815

DP-1 is a heterodimerization partner for members of the E2F family of transcription factors; E2F/DP-1 regulates the expression of various cellular promoters, particularly gene products that are involved in the cell cycle.

SIGNOR-253865

Q14186

Q01094

2

binding

up-regulates activity

0.815

The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family.In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3.

SIGNOR-240547

P28482

P35236

2

dephosphorylation

down-regulates activity

0.812

HePTP efficiently dephosphorylated active ERK2 on the tyrosine residue in the activation loop in vitro. Together, these data identify ERK2 as a specific and direct target of HePTP and are consistent with a model in which HePTP negatively regulates ERK2 activity as part of a feedback mechanism

SIGNOR-248484

P35236

P28482

2

phosphorylation

up-regulates activity

0.812

First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185.|

SIGNOR-249436

Q13651

P23458

2

phosphorylation

up-regulates activity

0.809

Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3).

SIGNOR-251338

P23458

Q13651

2

binding

up-regulates activity

0.809

Specifically, il-10 effects the activation of jak1 (associated with the il-10 receptor alpha Chain) and tyk2 (associated with the il-10 receptor beta Chain) and induces the activation of stat1, stat3, and, in some cells, stat5.

SIGNOR-68010

Q16539

P28562

2

dephosphorylation

down-regulates activity

0.805

The activity of MAPKs can be also regulated by a family of DUSPs (dual-specificity phosphatases)/MKPs (MAPK phosphatases), which dephosphorylate both phosphotyrosine and phosphothreonine residues MKPs 1, 4, 5 and 7 can dephosphorylate p38_ and p38_ in addition to JNK MAPKs. Importantly, some MKPs are transcriptionally up-regulated by stimuli that activate MAPK signalling, and are thought to play an important role limiting the extent of MAPK activation

SIGNOR-166571

P28482

P28562

2

dephosphorylation

down-regulates activity

0.805

We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively

SIGNOR-248465

P28562

P28482

2

phosphorylation

down-regulates

0.805

The dual-specificity mapk phosphatase mkp-1/cl100/dusp1 is an inducible nuclear protein controlled by p44/42 mapk (erk1/2) in a negative feedback mechanism to inhibit kinase activity. Here, we report on the molecular basis for a novel positive feedback mechanism to sustain erk activation by triggering mkp-1 proteolysis. Active erk2 docking to the def motif (fxfp, residues 339-342) of n-terminally truncated mkp-1 in vitro initiated phosphorylation at the ser(296)/ser(323) domain

SIGNOR-141593

P28562

Q16539

2

binding

up-regulates activity

0.805

Here we have shown that mkp-1 associates directly with p38 map kinase both in vivo and in vitro, and that this interaction enhances the catalytic activity of mkp-1. The point mutation asp-316-->asn in the c-terminus of p38, analogous to the erk2 (extracellular-signal-regulated kinase 2) sevenmaker mutation, dramatically decreases its binding to mkp-1 and substantially compromises its stimulatory effect on the catalytic activity of this phosphatase.

SIGNOR-83752

Q8TEP8

O14965

2

phosphorylation

up-regulates activity

0.796

Thus, following their sequential activation in Cep192 complexes, both AurA and Plx1 phosphorylate Cep192.|We found that Cep192 1\u20131000 -wt promoted AurA and Plx1 activation and itself underwent phosphorylation irrespective of whether it was bound to the endogenous or recombinant Plx1 (i.e. whether Plx1 was docked onto T46 or not) (lanes 6 and 8).

SIGNOR-279797

O14965

Q8TEP8

2

binding

up-regulates activity

0.796

These findings demonstrated that Cep192 mediates the AurA-Plk1 interaction and that the formation of the Cep192-AurA-Plk1 complex could be important for activating AurA and Plk1.

SIGNOR-266406

O14757

Q9HAW4

2

binding

up-regulates

0.794

Binding of claspin to xchk1 is highly elevated in the presence of dna templates that trigger a checkpoint arrest of the cell cycle in xenopus egg extracts

SIGNOR-84474

Q9HAW4

O14757

2

phosphorylation

up-regulates

0.794

We found that thr-916 on claspin is phosphorylated by chk1, suggesting that chk1 regulates claspin during checkpoint response.

SIGNOR-149411

Q06124

O60674

2

phosphorylation

up-regulates activity

0.793

Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2

SIGNOR-236266

O60674

Q06124

2

dephosphorylation

up-regulates quantity by stabilization

0.793

We report that SHP-2 dephosphorylates tyrosine (Tyr-1007) of Jak2 kinase, a critical recruitment site for the ubiquitin ligase-associated inhibitory protein suppressor of cytokine signaling-1 (SOCS-1), thereby contributing to Jak2 stability. Inactivation of SHP-2 function by blocking receptor/SHP-2 association or by using a catalytically inactive mutant of SHP-2 led to a marked increase in Jak2 ubiquitination/degradation, Jak2 phosphorylation on Tyr-1007, and Jak2/SOCS-1 association

SIGNOR-248665

Q9NR28

Q13489

2

ubiquitination

down-regulates quantity by destabilization

0.792

Here we show that cIAP1 and cIAP2 are E3 ubiquitin-protein isopeptide ligases (ubiquitin ligases) for Smac. cIAPs stimulate Smac ubiquitination both in vivo and in vitro, leading to Smac degradation. cIAP1 and cIAP2 associate with overlapping but distinct subsets of E2 (ubiquitin carrier protein) ubiquitin-conjugating enzymes. The substrate-dependent E3 activity of cIAPs is mediated by their RING domains and is dependent on the specific interactions between cIAPs and Smac.

SIGNOR-271391

Q13489

Q9NR28

2

binding

down-regulates quantity

0.792

Smac/diablo selectively causes the rapid degradation of c-iap1 and c-iap2 in hela cells. Smac binding to c-iap via its n-terminal iap-binding motif is the prerequisite for this effect

SIGNOR-121886

P02647

O95477

2

binding

up-regulates activity

0.79

The stimulation of cellular cholesterol and phospholipid efflux by apolipoprotein A-I is mediated by the activity of the ATP-binding cassette transporter A1 (ABCA1). ABCA1 forms a high affinity complex with apoA-I by binding amphipathic helices within the apolipoprotein. VFVNFA sequence is required for ABCA1 to form a complex with apoA-I and to transfer cholesterol to the apolipoprotein.

SIGNOR-252100

O95477

P02647

2

binding

up-regulates quantity by stabilization

0.79

ApoA-I stabilization of ABCA1 is mediated by reduced PEST sequence phosphorylation, which in turn leads to decreased calpain proteolysis of ABCA1.

SIGNOR-252101

Q96CV9

Q9UHD2

2

phosphorylation

up-regulates activity

0.789

Given that TBK1 can phosphorylate OPTN on S177, S473 and S513 in response to mitochondrial depolarization, we explored the function of these events in vivo.|Phosphorylation of OPTN on S473 and S513 promotes TBK1 activation and recruitment of OPTN to depolarized mitochondria.

SIGNOR-278170

Q9UHD2

Q96CV9

2

binding

up-regulates activity

0.789

Using biochemical experiments we showed that optineurin interacts with the protein kinase TBK1 and the ubiquitin ligase TRAF3. Furthermore, a mutation in optineurin that prevents the interaction with the small protein modifier ubiquitin (D474N) ablated the negative regulatory function of optineurin.

SIGNOR-262276

P18031

P06213

2

phosphorylation

up-regulates activity

0.788

Tyrosine residues 66, 152 and/or 153 of PTP1B are phosphorylated by the activated insulin receptor and are also necessary for formation of the PTP1B:insulin receptor complex| Furthermore, tyrosine phosphorylation of PTP1B by the insulin receptor tyrosine kinase increases the catalytic activity of PTP1B

SIGNOR-249370

P06213

P18031

2

dephosphorylation

down-regulates activity

0.788

Ptp1b is a protein tyrosine phosphatase that negatively regulates insulin sensitivity by dephosphorylating the insulin receptor.

SIGNOR-235499

Q6PGQ7

P53350

2

phosphorylation

down-regulates

0.788

Following cdk1-dependent recruitment, plk1 triggers hbora destruction by phosphorylating a recognition site for scf(beta-trcp).

SIGNOR-178154

P53350

Q6PGQ7

2

phosphorylation

up-regulates

0.788

Bora/aurora-a-dependent phosphorylation is a prerequisite for plk1 to promote mitotic entry after a checkpoint-dependent arrest.

SIGNOR-179425

Q6VVB1

O95278

2

binding

up-regulates activity

0.787

Here, we provide evidence indicating that the formation of the laforin–malin complex is positively regulated by AMPK. We show that laforin, but not malin, can interact physically with the catalytic subunit of AMPK and that purified AMPK phosphorylates GST::laforin in vitro.

SIGNOR-271729

O95278

Q6VVB1

2

polyubiquitination

down-regulates quantity by destabilization

0.787

Here, we demonstrate that malin is a single subunit E3 ubiquitin (Ub) ligase and that its RING domain is necessary and sufficient to mediate ubiquitination. Additionally, malin interacts with and polyubiquitinates laforin, leading to its degradation.

SIGNOR-271547

P28562

P27361

2

phosphorylation

up-regulates

0.786

Mkp-1 was a target in vivo and in vitro for p42(mapk) or p44(mapk), which phosphorylates mkp-1 on two carboxyl-terminal serine residues, serine 359 and serine 364. This phosphorylation did not modify mkp-1's intrinsic ability to dephosphorylate p44(mapk) but led to stabilization of the protein.

SIGNOR-73633

P27361

P28562

2

dephosphorylation

down-regulates activity

0.786

We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK, respectively

SIGNOR-248462

Q9HAT8

P51617

2

phosphorylation

up-regulates activity

0.781

The phosphorylation of Pellino2 by activated IRAK1 and IRAK4 could trigger and modulate the translocation of IRAKs from complex I to complex II.

SIGNOR-278947

P51617

Q9HAT8

2

ubiquitination

up-regulates

0.781

These studies suggest that pellino isoforms may be the e3 ubiquitin ligases that mediate the il-1-stimulated formation of k63-pub-irak1 in cells, which may contribute to the activation of ikkbeta and the transcription factor nf-kappab, as well as other pathways dependent on irak1/4.

SIGNOR-159058

Q9HAU4

Q15796

2

binding

up-regulates activity

0.778

We show that in the presence of TGF-beta signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases.Thus, stimulation by TGF-beta can induce the assembly of a Smad2-Smurf2 ubiquitin ligase complex that functions to target substrates for degradation.

SIGNOR-108490

Q15796

Q9HAU4

2

ubiquitination

down-regulates activity

0.778

The ability of smurf2 to promote smad2 destruction required the hect catalytic activity of smurf2 and depended on the proteasome-dependent pathway.

SIGNOR-236133

P49841

Q92837

2

binding

up-regulates

0.776

The frat family consists of three members: frat-1, -2, and -3. It has been shown that different sites of frat-1 interact with gsk-3 and dvl-1 and that wnt-1 disintegrates the complex formation of frat-1, dvl-1, and axin, resulting in the activation of the wnt signaling pathway

SIGNOR-58219

Q92837

P49841

2

phosphorylation

down-regulates activity

0.776

Protein kinase A (PKA) was found to phosphorylate Ser188 in vitro as well as in intact cells. Importantly, activation of endogenous cAMP-coupled beta-adrenergic receptors with norepinephrine stimulated the phosphorylation of FRAT1 at Ser188. GSK-3 was also able to phosphorylate FRAT1 at Ser188 and other residues in vitro or when overexpressed in intact cells. Phosphorylation of Ser188 by PKA inhibited the ability of FRAT1 to activate beta-catenin-dependent transcription.

SIGNOR-276057

P48357

O60674

2

phosphorylation

up-regulates activity

0.774

LRb signaling is initiated by leptin binding to the extracellular domain of the LRb dimer, leading to Jak2 transphosphorylation and activation. Activated Jak2 mediates the tyrosine phosphorylation of Tyr985 and Tyr1138of LRb. These phosphotyrosine residues immediately function as binding sites (double-ended lines) for SHP-2 and STAT3, both of which quickly become tyrosine-phosphorylated by Jak2.

SIGNOR-263494

O60674

P48357

2

binding

up-regulates activity

0.774

Janus kinase 2 (JAK2) is associated with LEPRb and autophosphorylates in response to leptin. JAK2 also phosphorylates LEPRb, STAT3, and multiple other downstream molecules.

SIGNOR-263491

P15391

P07948

2

phosphorylation

up-regulates

0.772

Experiments with purified proteins demonstrated that cd19-y513 was lyn's initial phosphorylation and binding site. This led to processive phosphorylation of cd19-y482, which recruited a second lyn molecule, allowing for transphosphorylation and amplification of lyn activation.

SIGNOR-80290

P07948

P15391

2

binding

up-regulates activity

0.772

CD19 has an extracellular region containing two C2-type Ig-like domains and a cytoplasmic region of ~240 amino acids with 9 conserved tyrosine residues24. Lyn, a Src-family protein tyrosine kinase member, is the dominant kinase that phosphorylates CD19 upon stimulation. Once tyrosyl-phosphorylated, CD19 serves as a membrane-bound adaptor protein for Src homology 2-containing signaling molecules such as Lyn, Vav, and phosphatidylinositol 3-kinase, which further mediate downstream activation cascades.

SIGNOR-242894

P45984

Q9UQF2

2

binding

down-regulates

0.769

These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins.

SIGNOR-70854

Q9UQF2

P45984

2

phosphorylation

up-regulates activity

0.769

Recruitment of jnk to jip1 and jnk-dependent jip1 phosphorylation regulates jnk module dynamics and activation it was observed that phosphorylation by jnk of jip1 on thr-103 and not other phosphorylated jip1 residues is necessary for the regulation of dlk association with jip1, dlk activation, and subsequent module activation.

SIGNOR-101201

Q96FA3

P51617

2

phosphorylation

up-regulates activity

0.767

In this article we demonstrate that pellino 1 is phosphorylated at multiple sites by irak1 or irak4 in vitro. The key residues involved in activation are located between residues 76 and 86 (ser-76, ser-78, thr-80, ser-82, and thr-86) and at thr-288 and ser-293, just n-terminal to the ring-like domain that carries the e3 ligase activity. Unusually, we found that the phosphorylation of ser-76 or thr-288 or ser-293 alone was sufficient for maximal activation

SIGNOR-96747

P51617

Q96FA3

2

ubiquitination

up-regulates quantity by expression

0.767

These results were consistent with the observations made in vitro, namely that pellino isoforms are activated by irak1-catalysed phosphorylation and that, once activated, can ubiquitinate irak1 in cells.

SIGNOR-159055

P00533

P18031

2

dephosphorylation

down-regulates activity

0.76

We have shown previously that amino acid residues flanking the phosphotyrosine are important for efficient PTP1 catalysis (Table 1 and Refs. 9, 10, and 17). For example, the kcat/Km value for the undecapeptide, EGFR988-989 (epidermal growth factor autophosphorylation site Tyr992, residues 988-998) (Asp-Ala-Asp-Glu-pTyr-Leu-Ile-Pro-Gln-Gln-Gly) is 3220-fold higher than that of phosphotyrosine (Table 1). We further demonstrated that a minimum of six amino acid residues are required for the most efficient PTP1 binding and catalysis.

SIGNOR-248407

P18031

P00533

2

phosphorylation

up-regulates

0.76

After binding to egfr, ptp1b becomes tyrosine-phosphorylated at tyr-66 phosphorylation of ptp1b by egfr enhances its catalytic activity

SIGNOR-52950