GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P06213	P42345	0	phosphorylation	up-regulates activity	0.391	Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.\|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR and InsR.	SIGNOR-280045
P20336	Q86UR5	0	relocalization	up-regulates activity	0.805	N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle	SIGNOR-264381
Q13546	O15111	0	phosphorylation	down-regulates activity	0.54	Indeed, IKKa and IKKb may directly repress RIPK1 kinase activity by addition of an inhibitory phosphate group on RIPK1.\|Mass spectrometry analysis of kinase assays performed with recombinant proteins allowed us to identify Ser166, Ser331, and Ser416 as highly conserved RIPK1 residues phosphorylated by IKKa and IKKb.	SIGNOR-278927
Q8N4C8	Q96MT3	1	phosphorylation	up-regulates activity	0.293	We show that Mink1 phosphorylates Prickle on a conserved threonine residue and regulates its Rab5-dependent endosomal trafficking, a process required for the localized plasma membrane accumulation and function of Prickle.	SIGNOR-263095
Q9UDY2	O00192	1	relocalization	down-regulates activity	0.369	We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression	SIGNOR-252122
Q96EP0	Q9Y6K9	1	polyubiquitination	up-regulates activity	0.849	Involvement of Gln271 and Asp275 of NEMO in LUBAC-mediated linear polyubiquitination.vHOIP NZF1 also recognizes NEMO, and this recognition is involved in linear polyubiquitination of NEMO. Linear chains conjugated to NEMO are recognized by NEMO in trans on another IKK complex, thereby inducing multimerization of the IKK complex and trans autophosphorylation of IKK2.	SIGNOR-272052
O14950	O43293	0	phosphorylation	up-regulates	0.511	Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.	SIGNOR-16043
Q9UKT8	Q86Y07	0	phosphorylation	down-regulates activity	0.296	Collectively, CK1 and VRK2, but not GRK2 kinase, appears to mediate FBXW2 phosphorylation at the beta-TrCP binding motif.\|We followed this lead, and inactivated VRK2 and GRK2 by siRNA silencing, or CK1 and VRK2 by small molecule inhibitor IC-261, and found that GRK2 knockdown had no effect, whereas CK1 and VRK2 inhibition or VRK2 silencing largely blocked the degradation of exogenously expressed FBXW2 (XREF_FIG and XREF_SUPPLEMENTARY).	SIGNOR-280161
P06241	P54646	1	phosphorylation	down-regulates activity	0.257	Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.	SIGNOR-277279
O14672	P35070	1	cleavage	up-regulates activity	0.372	Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin	SIGNOR-259839
Q96BR1	Q13045	1	phosphorylation	up-regulates	0.355	Here we show that flii is an in vivo substrate of cisk that functions downstream of pi 3-kinase. Cisk can associate with flii and phosphorylate flii at residues ser(436) and thr(818).We demonstrate here that cisk can enhance er transcription, which is dependent on its kinase activity, and mutation of cisk phosphorylation sites on flii attenuates its activity as an er co-activator.	SIGNOR-184688
P27361	P84022	1	phosphorylation	down-regulates	0.623	These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3.	SIGNOR-66781
Q13233	Q13153	0	phosphorylation	up-regulates activity	0.538	We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation.	SIGNOR-236006
Q13315	O15151	1	phosphorylation	down-regulates quantity by destabilization	0.735	Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm.	SIGNOR-149296
Q9BXM7	Q6NUN9	1	phosphorylation	up-regulates activity	0.37	PINK1 directly phosphorylates PARIS at S322 and S613, priming it for ubiquitination by Parkin, which interacts with the C-terminus zinc finger of PARIS and tags it for destruction [ xref \u2013 xref , xref ].\|Thus, by tagging PARIS for destruction, PINK1/Parkin drive the generation of new mitochondria by increasing PGC-1\u03b1 levels (Fig. 1d).	SIGNOR-278268
P55211	P00519	0	phosphorylation	up-regulates	0.513	C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.	SIGNOR-133260
O00141	Q9BUB5	1	phosphorylation	down-regulates activity	0.2	We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity.	SIGNOR-277357
P49841	P38936	1	phosphorylation	down-regulates quantity by destabilization	0.4	Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation	SIGNOR-152941
Q00535	P50613	0	phosphorylation	up-regulates activity	0.517	In addition, the Cdk7 substrate, CTD of RNAPII, causes a dose-dependent decline in Cdk5 activation by Cdk7.\|Likewise, Cdk7 or cyclin H immunoprecipitate from mouse brain specifically phosphorylates wt Cdk5 at Ser159 and enhances Cdk5 and p25 activity.	SIGNOR-278923
P28482	Q9UQ13	1	phosphorylation	down-regulates quantity by destabilization	0.322	Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.	SIGNOR-277442
Q96PU5	O15527	1	ubiquitination	down-regulates quantity by destabilization	0.2	We demonstrate that recombinant NEDD4L stimulates ubiquitylation of OGG1 in vitro, particularly on lysine 341, and that NEDD4L and OGG1 interact in U2OS cells.	SIGNOR-278639
Q16665	P29375	1	transcriptional regulation	up-regulates quantity by expression	0.273	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-271565
P45452	P02679	1	cleavage	down-regulates quantity by destabilization	0.2	Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII\| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.\|MMP-13 27YVATRDN g-chain\| 20ADSGEGD a-chain\| 124RNSVDXLNXN b-chain\| 442LRTGKEKV a-chain	SIGNOR-263614
P03372	P12931	0	phosphorylation	up-regulates	0.778	Although the molecular mechanisms underlying ligand-independent activation of era are not completely understood, phosphorylation of a serine residue in af1 has been implicated in the response to epidermal growth factor. Era is also a target for tyrosine phosphorylation, anda single tyrosine residue located immediately adjacent to af2 has been identified as a substrate for src-family tyrosine kinases.	SIGNOR-55857
P24941	P17480	1	phosphorylation	up-regulates activity	0.372	Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity	SIGNOR-235419
Q7KZI7	P10636-2	1	phosphorylation	down-regulates activity	0.707	We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.	SIGNOR-275437
P36406	O14920	0	phosphorylation	down-regulates activity	0.287	Phosphorylation of ARD1 by IKKbeta reduced its growth suppression effect.	SIGNOR-279337
O95835	Q16635	1	phosphorylation	down-regulates activity	0.387	When the inhibitory Hippo kinase module is ' on ', LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.\|When the inhibitory Hippo kinase module is \u2018on\u2019, LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.	SIGNOR-279200
P78536	O14944	1	cleavage	up-regulates activity	0.565	ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF	SIGNOR-259843
O43561	P18031	0	dephosphorylation	down-regulates activity	0.504	Using a pharmacological inhibitor, we provide evidence that PTP1B activation and LAT dephosphorylation processes were required for irreversible platelet aggregation.\|In collagen-stimulated platelets, the signaling complexes recruited by tyrosine-phosphorylated LAT are essential for PLCgamma2 activation	SIGNOR-248403
Q96GM5	Q96EP1	0	polyubiquitination	down-regulates quantity by destabilization	0.307	Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.	SIGNOR-271459
P53667	P23528	1	phosphorylation	down-regulates	0.814	Our results suggest that limk1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis	SIGNOR-159885
Q6ZMZ0	Q9NWZ5	1	ubiquitination	down-regulates quantity by destabilization	0.583	We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and has as one of its substrates, URKL-1, thus defining this cytolytic protein as an E3 ubiquitin ligase.	SIGNOR-271590
P27361	P14598	1	phosphorylation	up-regulates	0.42	Upon activation, several serine residues on the cytosolic oxidase subunit p47phox become phosphorylated. Mitogen-activated protein kinase phophorylated only the peptide containing ser345/348.	SIGNOR-40821
P08559	Q9P0J1	0	dephosphorylation	up-regulates activity	0.732	Sites 1, 2, and 3 were dephosphorylated either individually or in the presence of the other sites by the phospho-E1-phosphatase resulting in complete reactivation of the E1. The rates of dephosphorylation and reactivation were similar for sites 1, 2, and 3, indicating a random dephosphorylation mechanism	SIGNOR-252055
P35637	Q9Y566	1	post transcriptional regulation	up-regulates quantity	0.2	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.\|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.	SIGNOR-262104
P17612	P60983	1	phosphorylation	up-regulates activity	0.307	Protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. PKA is capable of phosphorylating threonine 26 and serine 82.	SIGNOR-249983
P07384	Q15078	1	cleavage	up-regulates activity	0.571	Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain	SIGNOR-251583
Q9Y5T5	P33981	0	phosphorylation	down-regulates quantity by destabilization	0.37	Usp16 is a TTK phosphorylation substrate.	SIGNOR-277351
Q8IXL6	P07237	1	phosphorylation	up-regulates activity	0.387	The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.	SIGNOR-275574
P12931	P23469	0	dephosphorylation	up-regulates activity	0.402	PTPepsilonM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src.	SIGNOR-238074
Q05397	Q5S007	0	phosphorylation	down-regulates activity	0.2	LRRK2 inhibits FAK activation in a kinase dependent manner, meaning that the G2019S gain-of-function mutation results in the excessive inhibition of FAK activation and microglial motility.\|Taken together, these results suggest that LRRK2 directly phosphorylate FAK at T474.	SIGNOR-278281
P27361	O75676	1	phosphorylation	up-regulates	0.586	Rsk-b is a p38alphamapk substrate, and activated by p38alphamapk and, more weakly, by erk1	SIGNOR-60998
P27987	P17252	0	null	down-regulates activity	0.359	However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.	SIGNOR-248990
P08263	Q16236	0	transcriptional regulation	up-regulates quantity by expression	0.342	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256278
Q9UJU6	P43403	0	phosphorylation	up-regulates	0.64	We found an interaction between the tyrosine kinase zap-70 and hip-55, which was induced by tcr stimulation. Zap-70 phosphorylated hip-55 at tyr-334 and tyr-344, which were shown to be the tyrosine phosphorylation sites of hip-55 in stimulated t cells.Our results demonstrate for the first time that hip-55 is an important adaptor protein for the jnk kinase cascade in tcr signaling.	SIGNOR-118695
Q00535	P16220	1	phosphorylation	up-regulates activity	0.374	CDK5 Activates the Self-Renewal Regulator CREB1 in GSCs.\|Our data indicate that CDK5, which has previously been shown to activate CREB1 through cAMP and PKA in dopamine neurons present in the ventral tegmental area, can directly bind with and phosphorylate CREB1 in a PKA and cAMP independent manner, at least in GSCs.	SIGNOR-279682
P51955	P36873	1	phosphorylation	down-regulates	0.488	Pp1 is a substrate for nek2 and phosphorylation of pp1gamma(1) on two c-terminal sites reduces its phosphatase activity.	SIGNOR-78603
P18031	P04629	1	dephosphorylation	down-regulates activity	0.378	PTP1B inactivation prevents TrkA exit from soma and causes receptor degradation, suggesting a " gate-keeper " mechanism that ensures targeting of inactive receptors to axons to engage with ligand.\|We identify a gate keeping mechanism in which TrkA receptors, destined for transcytosis, are dephosphorylated in neuronal soma by the ER-resident tyrosine phosphatase, PTP1B.	SIGNOR-277081
P35222	O14965	0	phosphorylation	up-regulates quantity	0.346	In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic \u03b2-catenin expression in esophageal squamous cell carcinoma tissues.\|We also demonstrate for the first time that Aurora-A directly interacts with \u03b2-catenin and phosphorylates \u03b2-catenin at Ser552 and Ser675.	SIGNOR-278468
Q8WVD3	P06493	0	phosphorylation	up-regulates activity	0.2	Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.	SIGNOR-277832
P12931	Q14790	1	phosphorylation	down-regulates	0.453	Src kinase phosphorylates caspase-8 on tyr380: a novel mechanism of apoptosis suppressionwe identified caspase-8 as a new substrate for src kinase. Phosphorylation occurs on tyr380, situated in the linker region between the large and the small subunits of human procaspase-8, and results in downregulation of caspase-8 proapoptotic function	SIGNOR-146127
Q8TDC3	P30307	1	phosphorylation	down-regulates	0.483	Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3	SIGNOR-56473
Q15256	P40763	1	dephosphorylation	down-regulates activity	0.2	Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.	SIGNOR-248719
Q9BQQ3	P06493	0	phosphorylation	down-regulates activity	0.715	Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.	SIGNOR-262840
Q9BXL7	Q9UNE7	0	ubiquitination	up-regulates activity	0.327	Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation.	SIGNOR-278720
P62805	Q8TDB6	0	monoubiquitination	down-regulates activity	0.2	Herein, we demonstrate that BBAP selectively monoubiquitylates histone H4 lysine 91 and protects cells exposed to DNA-damaging agents. Disruption of BBAP-mediated monoubiquitylation of histone H4K91 is associated with the loss of chromatin-associated H4K20 methylase, mono- and dimethyl H4K20, and a delay in the kinetics of 53BP1 foci formation at sites of DNA damage. In response to DNA damage, BBAP expression increases and the E3 ligase selectively monoubiquitylates H4K91. Disruption of BBAP-mediated monoubiquitylation of H4K91 is associated with loss of chromatin-associated PR-Set7/Set8 and mono- and dimethyl H4K20, delayed kinetics of 53BP1 foci formation and increased sensitivity to DNA damage.	SIGNOR-271897
P28482	O95997	1	phosphorylation	up-regulates	0.353	Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function.	SIGNOR-79515
P28482	Q9UHB6	1	phosphorylation	down-regulates quantity by destabilization	0.2	Mechanistic study revealed that EGF could activate the phosphorylation, ubiquitination, and degradation of EPLIN through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent signaling cascade. Pharmacological inhibition of the ERK1/2 pathway effectively antagonized EGF-induced EPLIN degradation. Two serine residues, i.e. serine 362 and serine 604, were identified as putative ERK1/2 phosphorylation sites in human EPLIN, whose point mutation rendered resistance to EGF-induced protein turnover.	SIGNOR-263054
P10275	Q9UNE7	0	ubiquitination	down-regulates quantity by destabilization	0.478	Via this mechanism, CHIP ubiquitinates and degrades glucocorticoid receptor (GR), androgen receptor (AR), estrogen receptor (ER), ErbB2, and alpha-synuclein, only when bound to Hsp .	SIGNOR-278782
O43791	Q9UER7	1	ubiquitination	down-regulates quantity	0.483	These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.	SIGNOR-268858
P06241	Q9Y6K9	1	phosphorylation	down-regulates activity	0.357	Either IKKγ/NEMO WT or the Y374F mutant was coexpressed with each member of the Src family protein tyrosine kinases (SF-PTKs) in HEK 293T cells. Our study thus demonstrates that the Y374 or S377 residue located at the C-terminal proline-rich domain of human IKKγ/NEMO undergoes phosphorylation upon TNF-α treatment or KvFLIP expression, respectively, resulting in the suppression of IKKγ/NEMO activity to induce NF-κB activation.	SIGNOR-276371
P62820	O75385	1	relocalization	up-regulates activity	0.532	C9orf72 acts as an effector of Rab1a that recruits active Rab1a to theULK1 complex to promote translocation of the ULK1 complex to thephagophore during autophagy initiation	SIGNOR-261299
P00533	Q96TA1	1	phosphorylation	up-regulates activity	0.2	We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras.	SIGNOR-273637
Q9UH17	P17612	0	phosphorylation	down-regulates activity	0.2	Here we show that protein kinase A (PKA) physically binds to A3B and phosphorylates Thr214.	SIGNOR-277455
O15297	P19484	0	transcriptional regulation	up-regulates quantity by expression	0.2	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276557
P18031	P53350	0	phosphorylation	up-regulates activity	0.354	Cdk1-cyclin B1 directly phosphorylates PTP1B at serine 386 in a kinase assay. Recombinant Plk1 phosphorylates PTP1B on serine 286 and 393 in vitro, however, it requires a priming phosphorylation by Cdk1 at serine 386 highlighting a novel co-operation between Cdk1 and Plk1 in the regulation of PTP1B.\|Finally, phosphorylation on serine 286 enhanced PTP1B phosphatase activity.	SIGNOR-272990
P54762	P45985	1	relocalization	up-regulates activity	0.2	The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.	SIGNOR-275922
P42229	O14508	1	transcriptional regulation	up-regulates quantity by expression	0.668	We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling	SIGNOR-261547
P29966	P17252	0	phosphorylation	down-regulates activity	0.73	Here we report that MARCKS is a filamentous (F) actin crosslinking protein, with activity that is inhibited by PKC-mediated phosphorylation and by binding to calcium-calmodulin	SIGNOR-249650
Q9H4B4	P04637	1	phosphorylation	up-regulates activity	0.706	Upon exposure of cells to hydrogen peroxide (h(2)o(2)) phosphorylation of p53 was rapidly induced in human fibroblast gm00637, and this phosphorylation occurred on serine 9, serine 15, serine 20, but not on serine 392. In addition, h(2)o(2)-induced phosphorylation of p53 was followed by induction of p21, suggesting functional activation of p53. Ectopic expression of a plk3 dominant negative mutant, plk3(k52r), in gm00637 cells suppressed h(2)o(2)-induced serine 20 phosphorylation. Taken together, our studies strongly suggest that the oxidative stress-induced activation of p53 is at least in part mediated by plk3.	SIGNOR-109239
Q96EP0	P51843	1	monoubiquitination	up-regulates quantity by stabilization	0.437	RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1.	SIGNOR-271786
P54646	Q00535	0	phosphorylation	down-regulates activity	0.216	In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.\|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site.	SIGNOR-280218
P19525	Q9UQ80	1	phosphorylation	up-regulates activity	0.243	Ebp1 itself is phosphorylated by the PKR protein kinase, suggesting that the effects of Ebp1 overexpression evidenced in vivo on eIF2alpha phosphorylation could be achieved by competition between Ebp1 and eIF2alpha for PKR kinase activity.	SIGNOR-279170
Q01543	Q05655	0	phosphorylation	down-regulates	0.346	We have previously demonstrated that in response to transforming growth factor _ (tgf_), fli-1 activity is repressed through a series of sequential posttranslational modifications, consisting of protein kinase c_ (pkc_)-induced thr312 phosphorylation, acetylation by p300/creb binding protein-associated factor, and detachment from the collagen promoter.	SIGNOR-172113
Q53ET0	P54646	0	phosphorylation	down-regulates	0.489	Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2	SIGNOR-142211
P51813	P25116	1	phosphorylation	down-regulates activity	0.2	As shown in xref \u2013 xref , BMX overexpression increased PAR1-WT phosphorylation but had no effect on PAR1 Y 381 FY 383 F mutant, indicating that BMX phosphorylated PAR1 at Y 381 and Y 383 .\|Mechanically , BMX represses PAR1 signaling in ECs by promoting PAR1 phosphorylation and internalization .	SIGNOR-279593
P05771	P06400	1	phosphorylation	down-regulates activity	0.352	The exact mechanism by which PKCbeta degrades RB is unknown.\|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).	SIGNOR-280083
P09693	P06239	0	phosphorylation	up-regulates activity	0.56	Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex.	SIGNOR-259931
P48729	P98177	1	phosphorylation	down-regulates	0.2	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.	SIGNOR-183664
P28482	P10275	1	phosphorylation	down-regulates	0.511	Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126	SIGNOR-178718
Q16539	P03372	1	phosphorylation	up-regulates	0.625	Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells	SIGNOR-136950
P31749	Q92879	1	phosphorylation	up-regulates activity	0.41	In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.	SIGNOR-280173
P06241	Q13291	1	phosphorylation	up-regulates activity	0.658	All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327.	SIGNOR-251182
P05771-2	P67775	0	dephosphorylation	down-regulates activity	0.446	Inhibition of PP2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of PKCbetaII isoform	SIGNOR-248621
Q9HBH9	P42345	0	phosphorylation	down-regulates activity	0.274	MTOR phosphorylates MNK2a on Ser74. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G.	SIGNOR-277516
Q13153	Q99426	1	phosphorylation	up-regulates	0.448	P21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor b. Pak1 directly phosphorylated tcob in vitro and in vivo on serines 65 and 128 and colocalized with tcob on newly polymerized microtubules and on centrosomes. Pak1 phosphorylation is necessary for normal tcob function	SIGNOR-135464
Q9BSA4	Q96PU5	0	polyubiquitination	down-regulates quantity by destabilization	0.286	Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein.	SIGNOR-272632
P06239	P51692	1	phosphorylation	up-regulates activity	0.643	A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation.\|Expression of the active Lck kinase induces both tyrosine phosphorylation and DNA binding activity of signal transducer and activator of transcription 5b (STAT5b), a STAT family member activated in a variety of tumor cells.	SIGNOR-279056
O60285	O14974	1	phosphorylation	down-regulates	0.507	Phosphorylation of ser(445), ser(472), and ser(910) of mypt1 by nuak1 promoted the interaction of mypt1 with 14-3-3 adaptor proteins, thereby suppressing phosphatase activity.	SIGNOR-164747
P01116	P17706	0	dephosphorylation	down-regulates activity	0.276	Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling.	SIGNOR-277039
P78527	Q96SD1	1	phosphorylation	up-regulates	0.699	Artemis is a nuclear phosphoprotein required for genomic integrity whose phosphorylation is increased subsequent to dna damage. Artemis phosphorylation by the dna-dependent protein kinase (dna-pk). However, regardless of its association with dna-pkcs, phosphorylation of artemis at both s516 and s645 was stimulated in response to the double-stranded dna-damaging agent bleomycin	SIGNOR-148327
P25098	P18545	1	phosphorylation	up-regulates activity	0.2	Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.	SIGNOR-247823
Q9GZM8	P60510	0	dephosphorylation	down-regulates activity	0.395	Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation\|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.\|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219	SIGNOR-248550
P12931	P63244	1	phosphorylation	up-regulates	0.2	We found that rack1 is a src substrate. Moreover, src activity is necessary for both the tyrosine phosphorylation of rack1 and the binding of rack1 to src's sh2 domain that occur following pkc activation. To identify the tyrosine(s) on rack1 that is phosphorylated by src, we generated and tested a series of rack1 mutants. We found that src phosphorylates rack1 on tyr 228 and/or tyr 246	SIGNOR-94800
Q9UL17	P60568	1	transcriptional regulation	down-regulates quantity by repression	0.473	T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells	SIGNOR-266233
Q13422	P62140	0	dephosphorylation	up-regulates	0.265	Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway	SIGNOR-174862
Q14738	P17612	0	phosphorylation	up-regulates	0.2	Protein kinase a activates protein phosphatase 2a by phosphorylation of the b56delta subunit.	SIGNOR-153218
O95239	O14965	0	phosphorylation	up-regulates activity	0.419	We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).	SIGNOR-265993
Q13315	Q99801	1	phosphorylation	down-regulates quantity by destabilization	0.362	ATM phosphorylates NKX3.1 on T166 and then T134, resulting in NKX3.1 ubiquitination and degradation resulting from an apparent regulatory interaction.	SIGNOR-276499

P06213

P42345

0

phosphorylation

up-regulates activity

0.391

Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively.|Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR and InsR.

SIGNOR-280045

P20336

Q86UR5

0

relocalization

up-regulates activity

0.805

N-terminal interactions of RIMs with RAB3 and MUNC13 regulate DCV fusion. Through N-terminal interactions, RIMs position MUNC13 and recruit DCVs via RAB3, which is located on the vesicle

SIGNOR-264381

Q13546

O15111

0

phosphorylation

down-regulates activity

0.54

Indeed, IKKa and IKKb may directly repress RIPK1 kinase activity by addition of an inhibitory phosphate group on RIPK1.|Mass spectrometry analysis of kinase assays performed with recombinant proteins allowed us to identify Ser166, Ser331, and Ser416 as highly conserved RIPK1 residues phosphorylated by IKKa and IKKb.

SIGNOR-278927

Q8N4C8

Q96MT3

1

phosphorylation

up-regulates activity

0.293

We show that Mink1 phosphorylates Prickle on a conserved threonine residue and regulates its Rab5-dependent endosomal trafficking, a process required for the localized plasma membrane accumulation and function of Prickle.

SIGNOR-263095

Q9UDY2

O00192

1

relocalization

down-regulates activity

0.369

We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression

SIGNOR-252122

Q96EP0

Q9Y6K9

1

polyubiquitination

up-regulates activity

0.849

Involvement of Gln271 and Asp275 of NEMO in LUBAC-mediated linear polyubiquitination.vHOIP NZF1 also recognizes NEMO, and this recognition is involved in linear polyubiquitination of NEMO. Linear chains conjugated to NEMO are recognized by NEMO in trans on another IKK complex, thereby inducing multimerization of the IKK complex and trans autophosphorylation of IKK2.

SIGNOR-272052

O14950

O43293

0

phosphorylation

up-regulates

0.511

Hzipk phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. Phosphorylation of mrlc is required to generate the driving force in the migration of the cells but not necessary for localization of myosin ii at the leading edge.

SIGNOR-16043

Q9UKT8

Q86Y07

0

phosphorylation

down-regulates activity

0.296

Collectively, CK1 and VRK2, but not GRK2 kinase, appears to mediate FBXW2 phosphorylation at the beta-TrCP binding motif.|We followed this lead, and inactivated VRK2 and GRK2 by siRNA silencing, or CK1 and VRK2 by small molecule inhibitor IC-261, and found that GRK2 knockdown had no effect, whereas CK1 and VRK2 inhibition or VRK2 silencing largely blocked the degradation of exogenously expressed FBXW2 (XREF_FIG and XREF_SUPPLEMENTARY).

SIGNOR-280161

P06241

P54646

1

phosphorylation

down-regulates activity

0.257

Here we identified that Fyn phosphorylates the α subunit of AMPK on Y436 and inhibits AMPK enzymatic activity without altering the assembly state of the AMPK heterotrimeric complex.

SIGNOR-277279

O14672

P35070

1

cleavage

up-regulates activity

0.372

Like ADAM17, ADAM10 has also been implicated in the activation of specific EGFR ligands, especially EGF and betacellulin

SIGNOR-259839

Q96BR1

Q13045

1

phosphorylation

up-regulates

0.355

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

SIGNOR-184688

P27361

P84022

1

phosphorylation

down-regulates

0.623

These results suggest that oncogenic ras, acting through mek1 and erk kinases, induces the phosphorylation of smad2 and smad3.

SIGNOR-66781

Q13233

Q13153

0

phosphorylation

up-regulates activity

0.538

We found that pak1 phosphorylated mekk1 on serine 67 of its amino-terminal regulatory domain. mekk1 activity was increased modestly following pak phosphorylation.

SIGNOR-236006

Q13315

O15151

1

phosphorylation

down-regulates quantity by destabilization

0.735

Recently we showed that atm- and hdm2-dependent ubiquitination and subsequent degradation of hdmx following dsb induction are mediated by phosphorylation of hdmx on s403, s367, and s342, with s403 being targeted directly by atm.

SIGNOR-149296

Q9BXM7

Q6NUN9

1

phosphorylation

up-regulates activity

0.37

PINK1 directly phosphorylates PARIS at S322 and S613, priming it for ubiquitination by Parkin, which interacts with the C-terminus zinc finger of PARIS and tags it for destruction [ xref \u2013 xref , xref ].|Thus, by tagging PARIS for destruction, PINK1/Parkin drive the generation of new mitochondria by increasing PGC-1\u03b1 levels (Fig. 1d).

SIGNOR-278268

P55211

P00519

0

phosphorylation

up-regulates

0.513

C-abl phosphorylates casp9 on tyr-153 in vitro and in vivo in response to dna damage.The Present results demonstrate that c-abl binds directly to casp9.

SIGNOR-133260

O00141

Q9BUB5

1

phosphorylation

down-regulates activity

0.2

We show that SGK1 phosphorylates MNK1 at a conserved site, which represses its activity.

SIGNOR-277357

P49841

P38936

1

phosphorylation

down-regulates quantity by destabilization

0.4

Glycogen synthase kinase 3beta phosphorylates p21waf1/cip1 for proteasomal degradation after uv irradiationhere, we show that ser-114 phosphorylation of p21 protein by glycogen synthase kinase 3beta (gsk-3beta) is required for its degradation in response to uv irradiation

SIGNOR-152941

Q00535

P50613

0

phosphorylation

up-regulates activity

0.517

In addition, the Cdk7 substrate, CTD of RNAPII, causes a dose-dependent decline in Cdk5 activation by Cdk7.|Likewise, Cdk7 or cyclin H immunoprecipitate from mouse brain specifically phosphorylates wt Cdk5 at Ser159 and enhances Cdk5 and p25 activity.

SIGNOR-278923

P28482

Q9UQ13

1

phosphorylation

down-regulates quantity by destabilization

0.322

Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.

SIGNOR-277442

Q96PU5

O15527

1

ubiquitination

down-regulates quantity by destabilization

0.2

We demonstrate that recombinant NEDD4L stimulates ubiquitylation of OGG1 in vitro, particularly on lysine 341, and that NEDD4L and OGG1 interact in U2OS cells.

SIGNOR-278639

Q16665

P29375

1

transcriptional regulation

up-regulates quantity by expression

0.273

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-271565

P45452

P02679

1

cleavage

down-regulates quantity by destabilization

0.2

Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and membrane type 1-matrix metalloproteinase impair clotting by degradation of fibrinogen and factor XII| We have now investigated the role of collagenase-2 (MMP-8), macrophage elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor XII of the plasma clotting system.|MMP-13 27YVATRDN g-chain| 20ADSGEGD a-chain| 124RNSVDXLNXN b-chain| 442LRTGKEKV a-chain

SIGNOR-263614

P03372

P12931

0

phosphorylation

up-regulates

0.778

Although the molecular mechanisms underlying ligand-independent activation of era are not completely understood, phosphorylation of a serine residue in af1 has been implicated in the response to epidermal growth factor. Era is also a target for tyrosine phosphorylation, anda single tyrosine residue located immediately adjacent to af2 has been identified as a substrate for src-family tyrosine kinases.

SIGNOR-55857

P24941

P17480

1

phosphorylation

up-regulates activity

0.372

Phosphorylation of ubf at serine 388 is required for interaction with rna polymerase i and activation of rdna transcription. After g(1) progression ubf is phosphorylated at serine 388 by cdk2/cyclin e and cdk2/cyclin a. Conversion of serine 388 to glycine abolishes ubf activity

SIGNOR-235419

Q7KZI7

P10636-2

1

phosphorylation

down-regulates activity

0.707

We have studied the relationship between the phosphorylation oftau by several kinases (MARK, PKA, MAPK, GSK3) and its assembly into PHFs. By contrast, MARK and PKA phosphorylate several sites within the repeats (notably theKXGS motifs including Ser262, Ser324, and Ser356, plus Ser320); in addition PKA phosphorylates somesites in the flanking domains, notably Ser214. This type of phosphorylation strongly reduces tau’s affinityfor microtubules, and at the same time inhibits tau’s assembly into PHFs.

SIGNOR-275437

P36406

O14920

0

phosphorylation

down-regulates activity

0.287

Phosphorylation of ARD1 by IKKbeta reduced its growth suppression effect.

SIGNOR-279337

O95835

Q16635

1

phosphorylation

down-regulates activity

0.387

When the inhibitory Hippo kinase module is ' on ', LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.|When the inhibitory Hippo kinase module is \u2018on\u2019, LATS1 and LATS2 phosphorylate and inactivate YAP and TAZ, and the output gene production is therefore turned off.

SIGNOR-279200

P78536

O14944

1

cleavage

up-regulates activity

0.565

ADAM17 is involved in the release and activation of several growth factors and cytokine receptor ligands. Among the growth factors activated by ADAM17 are TGF-alpha, amphiregulin, epiregulin and HB-EGF

SIGNOR-259843

O43561

P18031

0

dephosphorylation

down-regulates activity

0.504

Using a pharmacological inhibitor, we provide evidence that PTP1B activation and LAT dephosphorylation processes were required for irreversible platelet aggregation.|In collagen-stimulated platelets, the signaling complexes recruited by tyrosine-phosphorylated LAT are essential for PLCgamma2 activation

SIGNOR-248403

Q96GM5

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.307

Here we report that CHFR interacts with BRG1, SNF5, and BAF60a of the SWI/SNF-like BAF complex and ubiquitinates them to target for degradation through a proteasome-mediated pathway, and that SRG3/mBAF155 stabilizes these components by blocking their interaction with CHFR. These results suggest that CHFR enhances the degradation of the components of the SWI/SNF-like BAF complex by inducing their poly-ubiquitination.

SIGNOR-271459

P53667

P23528

1

phosphorylation

down-regulates

0.814

Our results suggest that limk1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis

SIGNOR-159885

Q6ZMZ0

Q9NWZ5

1

ubiquitination

down-regulates quantity by destabilization

0.583

We demonstrated that both UbcH7 and UbcH8 bind to full-length NKLAM. We demonstrated decreased protein expression and enhanced ubiquitination of URKL-1 in the presence of NKLAM. These data indicate that NKLAM is a RING finger protein that binds Ubcs and has as one of its substrates, URKL-1, thus defining this cytolytic protein as an E3 ubiquitin ligase.

SIGNOR-271590

P27361

P14598

1

phosphorylation

up-regulates

0.42

Upon activation, several serine residues on the cytosolic oxidase subunit p47phox become phosphorylated. Mitogen-activated protein kinase phophorylated only the peptide containing ser345/348.

SIGNOR-40821

P08559

Q9P0J1

0

dephosphorylation

up-regulates activity

0.732

Sites 1, 2, and 3 were dephosphorylated either individually or in the presence of the other sites by the phospho-E1-phosphatase resulting in complete reactivation of the E1. The rates of dephosphorylation and reactivation were similar for sites 1, 2, and 3, indicating a random dephosphorylation mechanism

SIGNOR-252055

P35637

Q9Y566

1

post transcriptional regulation

up-regulates quantity

0.2

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.|As seen in Figure 7 (top panel), both PSD-95 Q1-Q2 and Shank1a GQ probes pulled down endogenous FUS, whereas their M2 mutants did not, indicating that the GQ structure is sufficient for recognition.

SIGNOR-262104

P17612

P60983

1

phosphorylation

up-regulates activity

0.307

Protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regulated kinase (ERK) and enhancer of p38; both are subfamilies of mitogen-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascades. PKA is capable of phosphorylating threonine 26 and serine 82.

SIGNOR-249983

P07384

Q15078

1

cleavage

up-regulates activity

0.571

Calpains also modulate the activity of CDK5. Physiologically, CDK 5 is activated by p35 and its cleaved product p25. The latter has a longer half life than p35 and therefore it is a more potent activator of CDK5. The cleavage of p35 to p25 is mediated by calpain

SIGNOR-251583

Q9Y5T5

P33981

0

phosphorylation

down-regulates quantity by destabilization

0.37

Usp16 is a TTK phosphorylation substrate.

SIGNOR-277351

Q8IXL6

P07237

1

phosphorylation

up-regulates activity

0.387

The secretory pathway kinase Fam20C phosphorylates Ser357 of PDI and responds rapidly to various ER stressors. Phosphorylation of Ser357 induces an open conformation of PDI and turns it from a "foldase" into a "holdase", which is critical for preventing protein misfolding in the ER. Phosphorylated PDI also binds to the lumenal domain of IRE1α, a major UPR signal transducer, and attenuates excessive IRE1α activity.

SIGNOR-275574

P12931

P23469

0

dephosphorylation

up-regulates activity

0.402

PTPepsilonM activated c-Src kinase probably by directly dephosphorylating phospho-Tyr527, a negative regulatory site of c-Src.

SIGNOR-238074

Q05397

Q5S007

0

phosphorylation

down-regulates activity

0.2

LRRK2 inhibits FAK activation in a kinase dependent manner, meaning that the G2019S gain-of-function mutation results in the excessive inhibition of FAK activation and microglial motility.|Taken together, these results suggest that LRRK2 directly phosphorylate FAK at T474.

SIGNOR-278281

P27361

O75676

1

phosphorylation

up-regulates

0.586

Rsk-b is a p38alphamapk substrate, and activated by p38alphamapk and, more weakly, by erk1

SIGNOR-60998

P27987

P17252

0

null

down-regulates activity

0.359

However, when assayed in the presence of calcium/calmodulin, the activity of the B isoform was decreased following phosphorylation by either protein kinase.

SIGNOR-248990

P08263

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.342

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256278

Q9UJU6

P43403

0

phosphorylation

up-regulates

0.64

We found an interaction between the tyrosine kinase zap-70 and hip-55, which was induced by tcr stimulation. Zap-70 phosphorylated hip-55 at tyr-334 and tyr-344, which were shown to be the tyrosine phosphorylation sites of hip-55 in stimulated t cells.Our results demonstrate for the first time that hip-55 is an important adaptor protein for the jnk kinase cascade in tcr signaling.

SIGNOR-118695

Q00535

P16220

1

phosphorylation

up-regulates activity

0.374

CDK5 Activates the Self-Renewal Regulator CREB1 in GSCs.|Our data indicate that CDK5, which has previously been shown to activate CREB1 through cAMP and PKA in dopamine neurons present in the ventral tegmental area, can directly bind with and phosphorylate CREB1 in a PKA and cAMP independent manner, at least in GSCs.

SIGNOR-279682

P51955

P36873

1

phosphorylation

down-regulates

0.488

Pp1 is a substrate for nek2 and phosphorylation of pp1gamma(1) on two c-terminal sites reduces its phosphatase activity.

SIGNOR-78603

P18031

P04629

1

dephosphorylation

down-regulates activity

0.378

PTP1B inactivation prevents TrkA exit from soma and causes receptor degradation, suggesting a " gate-keeper " mechanism that ensures targeting of inactive receptors to axons to engage with ligand.|We identify a gate keeping mechanism in which TrkA receptors, destined for transcytosis, are dephosphorylated in neuronal soma by the ER-resident tyrosine phosphatase, PTP1B.

SIGNOR-277081

P35222

O14965

0

phosphorylation

up-regulates quantity

0.346

In addition, Aurora-A overexpression is significantly correlated with increased cytoplasmic \u03b2-catenin expression in esophageal squamous cell carcinoma tissues.|We also demonstrate for the first time that Aurora-A directly interacts with \u03b2-catenin and phosphorylates \u03b2-catenin at Ser552 and Ser675.

SIGNOR-278468

Q8WVD3

P06493

0

phosphorylation

up-regulates activity

0.2

Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.Altogether, our results suggest RNF138 is phosphorylated at position T27 in a CDK1- and CDK2-dependent manner.

SIGNOR-277832

P12931

Q14790

1

phosphorylation

down-regulates

0.453

Src kinase phosphorylates caspase-8 on tyr380: a novel mechanism of apoptosis suppressionwe identified caspase-8 as a new substrate for src kinase. Phosphorylation occurs on tyr380, situated in the linker region between the large and the small subunits of human procaspase-8, and results in downregulation of caspase-8 proapoptotic function

SIGNOR-146127

Q8TDC3

P30307

1

phosphorylation

down-regulates

0.483

Overexpression of hssad1 resulted in an increased phosphorylation of cdc25c on ser-216 in vivo.Phosphorylation of cdc25 triggers cell-cycle arrest by the sequestration of cdc25 by 14-3-3

SIGNOR-56473

Q15256

P40763

1

dephosphorylation

down-regulates activity

0.2

Here, we report identification of signal transducer and activator of transcription 3 (STAT3) as a substrate of PTPRT. Phosphorylation of a tyrosine at amino acid Y705 is essential for the function of STAT3, and PTPRT specifically dephosphorylated STAT3 at this position.

SIGNOR-248719

Q9BQQ3

P06493

0

phosphorylation

down-regulates activity

0.715

Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. Phosphorylation of Ser-277 is also dramatically increased during mitosis, however this is mediated by Cdk1 and not by ERK. These results argue against Ser-277 phosphorylation alone causing the dissolution of GRASP65 oligomers and cisternal unstacking, although it may make a significant contribution to these events.

SIGNOR-262840

Q9BXL7

Q9UNE7

0

ubiquitination

up-regulates activity

0.327

Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys 27 linked, which is important for CARMA1 mediated NF-kappaB activation.

SIGNOR-278720

P62805

Q8TDB6

0

monoubiquitination

down-regulates activity

0.2

Herein, we demonstrate that BBAP selectively monoubiquitylates histone H4 lysine 91 and protects cells exposed to DNA-damaging agents. Disruption of BBAP-mediated monoubiquitylation of histone H4K91 is associated with the loss of chromatin-associated H4K20 methylase, mono- and dimethyl H4K20, and a delay in the kinetics of 53BP1 foci formation at sites of DNA damage. In response to DNA damage, BBAP expression increases and the E3 ligase selectively monoubiquitylates H4K91. Disruption of BBAP-mediated monoubiquitylation of H4K91 is associated with loss of chromatin-associated PR-Set7/Set8 and mono- and dimethyl H4K20, delayed kinetics of 53BP1 foci formation and increased sensitivity to DNA damage.

SIGNOR-271897

P28482

O95997

1

phosphorylation

up-regulates

0.353

Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function.

SIGNOR-79515

P28482

Q9UHB6

1

phosphorylation

down-regulates quantity by destabilization

0.2

Mechanistic study revealed that EGF could activate the phosphorylation, ubiquitination, and degradation of EPLIN through an extracellular signal-regulated kinase 1/2 (ERK1/2)-dependent signaling cascade. Pharmacological inhibition of the ERK1/2 pathway effectively antagonized EGF-induced EPLIN degradation. Two serine residues, i.e. serine 362 and serine 604, were identified as putative ERK1/2 phosphorylation sites in human EPLIN, whose point mutation rendered resistance to EGF-induced protein turnover.

SIGNOR-263054

P10275

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.478

Via this mechanism, CHIP ubiquitinates and degrades glucocorticoid receptor (GR), androgen receptor (AR), estrogen receptor (ER), ErbB2, and alpha-synuclein, only when bound to Hsp .

SIGNOR-278782

O43791

Q9UER7

1

ubiquitination

down-regulates quantity

0.483

These results suggest that SPOP/Cul3-ubiquitin ligase plays an essential role in the control of Daxx level and, thus, in the regulation of Daxx-mediated cellular processes, including transcriptional regulation and apoptosis.

SIGNOR-268858

P06241

Q9Y6K9

1

phosphorylation

down-regulates activity

0.357

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

SIGNOR-276371

P62820

O75385

1

relocalization

up-regulates activity

0.532

C9orf72 acts as an effector of Rab1a that recruits active Rab1a to theULK1 complex to promote translocation of the ULK1 complex to thephagophore during autophagy initiation

SIGNOR-261299

P00533

Q96TA1

1

phosphorylation

up-regulates activity

0.2

We demonstrate here that activated EGFR phosphorylates the Y593 residue of the protein known as family with sequence similarity 129, member B (FAM129B), which is overexpressed in many types of human cancer. FAM129B phosphorylation increased the interaction between FAM129B and Ras, resulting in reduced binding of p120-RasGAP to Ras.

SIGNOR-273637

Q9UH17

P17612

0

phosphorylation

down-regulates activity

0.2

Here we show that protein kinase A (PKA) physically binds to A3B and phosphorylates Thr214.

SIGNOR-277455

O15297

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.2

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276557

P18031

P53350

0

phosphorylation

up-regulates activity

0.354

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

SIGNOR-272990

P54762

P45985

1

relocalization

up-regulates activity

0.2

The phosphorylated CNK1 interacts with ephrinB1. The binding of ephrinB1 to CNK1 connects RhoA and p115RhoGEF with ephrinB1-associated MKK4, promoting JNK activation and cell migration.

SIGNOR-275922

P42229

O14508

1

transcriptional regulation

up-regulates quantity by expression

0.668

We have also found SOCS2 and SOCS3 specifically induced in 32D/Flt3-ITD, both of which are STAT3/5 target genes and known negative regulators of receptor signaling

SIGNOR-261547

P29966

P17252

0

phosphorylation

down-regulates activity

0.73

Here we report that MARCKS is a filamentous (F) actin crosslinking protein, with activity that is inhibited by PKC-mediated phosphorylation and by binding to calcium-calmodulin

SIGNOR-249650

Q9H4B4

P04637

1

phosphorylation

up-regulates activity

0.706

Upon exposure of cells to hydrogen peroxide (h(2)o(2)) phosphorylation of p53 was rapidly induced in human fibroblast gm00637, and this phosphorylation occurred on serine 9, serine 15, serine 20, but not on serine 392. In addition, h(2)o(2)-induced phosphorylation of p53 was followed by induction of p21, suggesting functional activation of p53. Ectopic expression of a plk3 dominant negative mutant, plk3(k52r), in gm00637 cells suppressed h(2)o(2)-induced serine 20 phosphorylation. Taken together, our studies strongly suggest that the oxidative stress-induced activation of p53 is at least in part mediated by plk3.

SIGNOR-109239

Q96EP0

P51843

1

monoubiquitination

up-regulates quantity by stabilization

0.437

RNF31 promotes monoubiquitination of DAX-1 in an RBR domain-dependent manner. In conclusion, our results suggest that the major DAX-1 modification observed in different experimental settings is likely to be monoubiquitination at one or more lysine residues (multiubiquitination) possibly located within the LBD of DAX-1. RNF31 stabilizes endogenous DAX-1.

SIGNOR-271786

P54646

Q00535

0

phosphorylation

down-regulates activity

0.216

In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site.

SIGNOR-280218

P19525

Q9UQ80

1

phosphorylation

up-regulates activity

0.243

Ebp1 itself is phosphorylated by the PKR protein kinase, suggesting that the effects of Ebp1 overexpression evidenced in vivo on eIF2alpha phosphorylation could be achieved by competition between Ebp1 and eIF2alpha for PKR kinase activity.

SIGNOR-279170

Q01543

Q05655

0

phosphorylation

down-regulates

0.346

We have previously demonstrated that in response to transforming growth factor _ (tgf_), fli-1 activity is repressed through a series of sequential posttranslational modifications, consisting of protein kinase c_ (pkc_)-induced thr312 phosphorylation, acetylation by p300/creb binding protein-associated factor, and detachment from the collagen promoter.

SIGNOR-172113

Q53ET0

P54646

0

phosphorylation

down-regulates

0.489

Phosphorylation on the ser171 residue of crtc2 by ampk and ampk-related kinases, including the salt-inducible kinases (siks), is critical for determining the activity, cellular localization, and degradation of crtc2

SIGNOR-142211

P51813

P25116

1

phosphorylation

down-regulates activity

0.2

As shown in xref \u2013 xref , BMX overexpression increased PAR1-WT phosphorylation but had no effect on PAR1 Y 381 FY 383 F mutant, indicating that BMX phosphorylated PAR1 at Y 381 and Y 383 .|Mechanically , BMX represses PAR1 signaling in ECs by promoting PAR1 phosphorylation and internalization .

SIGNOR-279593

P05771

P06400

1

phosphorylation

down-regulates activity

0.352

The exact mechanism by which PKCbeta degrades RB is unknown.|To attribute increased RB phosphorylation specifically to PKC\u03b2, we transiently transfected PKC\u03b2 -/- hepatocytes, and reintroduction of PKC\u03b2 specifically resulted in increased in phospho-RB (Ser780) levels, further supporting that PKC\u03b2 phosphorylates RB specifically at Ser780 without affecting phosphorylation at other residues (Ser807 and Ser811) (Figure xref ).

SIGNOR-280083

P09693

P06239

0

phosphorylation

up-regulates activity

0.56

Last, we demonstrate directly that members of the CD3 complex, including the gamma, delta, and epsilon chains, as well as a putative zeta subunit, can be phosphorylated at tyrosine residues by the CD4/CD8.p56lck complex.

SIGNOR-259931

P48729

P98177

1

phosphorylation

down-regulates

0.2

Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.

SIGNOR-183664

P28482

P10275

1

phosphorylation

down-regulates

0.511

Map kinase-dependent phosphorylation at ar ser-515 was supported by the decrease in intensity of the slower migrating 23-kda band after treatment with both egf and increasing concentrations of the map kinase inhibitor, u0126

SIGNOR-178718

Q16539

P03372

1

phosphorylation

up-regulates

0.625

Conversely, constitutively active mkk6 induced p38 mapk activation that recapitulated the effects of polyphenols by inducing eralpha phosphorylation and downstream activation of akt, and enos. The key role of eralpha ser-118 phosphorylation was confirmed in enos-transfected cos-7 cells

SIGNOR-136950

P31749

Q92879

1

phosphorylation

up-regulates activity

0.41

In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.

SIGNOR-280173

P06241

Q13291

1

phosphorylation

up-regulates activity

0.658

All 3 tyrosines of CD150 (Tyr281, Tyr307, Tyr327) are phosphorylated by the src kinase Fyn. CD150 is unique among its homologues in the immunoglobulin superfamily in that it is able to bind SAP, a floating SH2 domain, in the absence of tyrosine phosphorylation. In this study, using a detailed mutagenesis mapping approach we have shown that SAP binding to CD150 is in fact bimodal. Prior to tyrosine phosphorylation, SAP binds the membrane-proximal motif surrounding Tyr281. Following tyrosine phosphorylation by tyrosine kinases such as Fyn, SAP binds additionally to the distal motif surrounding Tyr327.

SIGNOR-251182

P05771-2

P67775

0

dephosphorylation

down-regulates activity

0.446

Inhibition of PP2A increased phosphorylation at Ser660 that determines calcium sensitivity and activity of PKCbetaII isoform

SIGNOR-248621

Q9HBH9

P42345

0

phosphorylation

down-regulates activity

0.274

MTOR phosphorylates MNK2a on Ser74. Here, we show that mTORC1, a key regulator of mRNA translation and oncogenesis, directly phosphorylates MNK2 on Ser74. This suppresses MNK2 activity and impairs binding of MNK2 to eIF4G.

SIGNOR-277516

Q13153

Q99426

1

phosphorylation

up-regulates

0.448

P21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor b. Pak1 directly phosphorylated tcob in vitro and in vivo on serines 65 and 128 and colocalized with tcob on newly polymerized microtubules and on centrosomes. Pak1 phosphorylation is necessary for normal tcob function

SIGNOR-135464

Q9BSA4

Q96PU5

0

polyubiquitination

down-regulates quantity by destabilization

0.286

Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Nedd4-2 are binding partners and demonstrated that the TTYH2 PY motif is essential for these interactions. We have also shown that Nedd4-2-mediated ubiquitination of TTYH2 is a critical regulator of cell surface and total cellular levels of this protein.

SIGNOR-272632

P06239

P51692

1

phosphorylation

up-regulates activity

0.643

A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation.|Expression of the active Lck kinase induces both tyrosine phosphorylation and DNA binding activity of signal transducer and activator of transcription 5b (STAT5b), a STAT family member activated in a variety of tumor cells.

SIGNOR-279056

O60285

O14974

1

phosphorylation

down-regulates

0.507

Phosphorylation of ser(445), ser(472), and ser(910) of mypt1 by nuak1 promoted the interaction of mypt1 with 14-3-3 adaptor proteins, thereby suppressing phosphatase activity.

SIGNOR-164747

P01116

P17706

0

dephosphorylation

down-regulates activity

0.276

Mechanistically, PTPN2 negatively regulates tyrosine phosphorylation of KRAS, which, in turn, affects the activation KRAS and its downstream signaling.

SIGNOR-277039

P78527

Q96SD1

1

phosphorylation

up-regulates

0.699

Artemis is a nuclear phosphoprotein required for genomic integrity whose phosphorylation is increased subsequent to dna damage. Artemis phosphorylation by the dna-dependent protein kinase (dna-pk). However, regardless of its association with dna-pkcs, phosphorylation of artemis at both s516 and s645 was stimulated in response to the double-stranded dna-damaging agent bleomycin

SIGNOR-148327

P25098

P18545

1

phosphorylation

up-regulates activity

0.2

Mutation of Thr-62 (to Ala) in PDEgamma produced a GRK2 phosphorylation-resistant mutant that was less effective in associating with GRK2 in response to epidermal growth factor and did not potentiate the stimulation of p42/p44 mitogen-activated protein kinase by this growth factor.

SIGNOR-247823

Q9GZM8

P60510

0

dephosphorylation

down-regulates activity

0.395

Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219

SIGNOR-248550

P12931

P63244

1

phosphorylation

up-regulates

0.2

We found that rack1 is a src substrate. Moreover, src activity is necessary for both the tyrosine phosphorylation of rack1 and the binding of rack1 to src's sh2 domain that occur following pkc activation. To identify the tyrosine(s) on rack1 that is phosphorylated by src, we generated and tested a series of rack1 mutants. We found that src phosphorylates rack1 on tyr 228 and/or tyr 246

SIGNOR-94800

Q9UL17

P60568

1

transcriptional regulation

down-regulates quantity by repression

0.473

T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells

SIGNOR-266233

Q13422

P62140

0

dephosphorylation

up-regulates

0.265

Ikarosis dephosphorylated by protein phosphatase 1 (pp1) via interaction at a consensus pp1-binding motif/ hyperphosphorylation of ikaros promotes its degradation by the ubiquitin/proteasome pathway

SIGNOR-174862

Q14738

P17612

0

phosphorylation

up-regulates

0.2

Protein kinase a activates protein phosphatase 2a by phosphorylation of the b56delta subunit.

SIGNOR-153218

O95239

O14965

0

phosphorylation

up-regulates activity

0.419

We show that Aurora A phosphorylates the condensin I-dependent pool of KIF4A and thus actively promotes chromosome congression from the spindle poles to the metaphase plate. In vitro kinase assays showed that recombinant KIF4A can be phosphorylated by Aurora A and that this activity is inhibited by the specific Aurora A inhibitor MLN8537 (Fig. 7 C).

SIGNOR-265993

Q13315

Q99801

1

phosphorylation

down-regulates quantity by destabilization

0.362

ATM phosphorylates NKX3.1 on T166 and then T134, resulting in NKX3.1 ubiquitination and degradation resulting from an apparent regulatory interaction.

SIGNOR-276499