GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q86VB7	P67870	phosphorylation	up-regulates activity	0.307	Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. \| Inhibition studies using specific kinase inhibitors reveal that both CKII and PKC are involved in the CD163 signaling mechanism resulting in the secretion of proinflammatory cytokines.	SIGNOR-251056
P52945	P13010	binding	down-regulates quantity by destabilization	0.307	The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.	SIGNOR-225537
P05549	P54646	phosphorylation	up-regulates activity	0.307	Inhibition of AMPKalpha2 with either siRNA or compound C significantly suppressed the AngII- or nicotine enhanced AP-2alpha activity and the binding of AP-2alpha to DNA.\|We report that nicotine, a major component of cigarette smoke, activates AMPK in VSMCs and that AMPKalpha2 phosphorylates AP-2alpha at serine 219 resulting in aberrant expression of MMP2 and consequent AAA formation.	SIGNOR-279648
P00441	P14174	relocalization	down-regulates quantity by destabilization	0.307	Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells\|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein	SIGNOR-262797
Q16625	P05129	phosphorylation	up-regulates activity	0.307	Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.	SIGNOR-249107
O14813	P17612	phosphorylation	down-regulates	0.307	Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription.	SIGNOR-186462
Q9H2X6	P12931	phosphorylation	up-regulates activity	0.307	Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.\|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.	SIGNOR-278989
O14713	Q9UQM7	phosphorylation	up-regulates activity	0.307	The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited.	SIGNOR-250632
Q99538	Q9Y4K3	polyubiquitination	up-regulates quantity by stabilization	0.307	We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.	SIGNOR-272853
P61925	P00533	phosphorylation	up-regulates	0.307	The difference in inhibitory potency between pki_ and pki_ has been attributed to the absence of a tyrosine residue (tyr7) in pki_ that is present in the nh2-terminal region of pki_. This suggests that the absence of a single amino acid residue can result in variations in how the catalytic subunit of camp-dependent protein kinase interacts with pki which ultimately can result in alterations in pki inhibitory potency.	SIGNOR-22455
P05549	P68400	phosphorylation	up-regulates	0.307	Ck2 phosphorylates ap-2_ and increases its transcriptional activity	SIGNOR-175130
Q14847	P17612	phosphorylation	down-regulates activity	0.306	Lasp-1 binds to non-muscle filamentous (F) actin in vitro in a phosphorylation-dependent manner. Phosphorylation of recombinant lasp-1 with recombinant PKA increased the Kd and decreased the Bmax for lasp-1 binding to F-actin. PKA-dependent phosphorylation sites in rabbit lasp-1 to S99 and S146	SIGNOR-250074
Q13469	Q00987	ubiquitination	down-regulates quantity	0.306	MDM2 negatively regulates NFATc2 and T cell activation.\|The E3 ubiquitin ligase MDM2 is known to induce NFATc2 ubiquitination in a breast cancer cell line 24.	SIGNOR-278657
P01111	P49842	phosphorylation	up-regulates activity	0.306	STK19 Phosphorylates NRAS Protein at Serine 89\|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.\|	SIGNOR-264566
Q99717	Q13464	phosphorylation	up-regulates activity	0.306	The results showed that SMAD5 was directly phosphorylated at Ser463/465 by ROCK1 (Fig.\u00a04g).\|These data indicated that the activation of SMAD5 induced by TEM8 was mediated directly by the RhoC/ROCK1 pathway.To evaluate the effect of SMAD5 on the cellular functions of TEM8, SMAD5 was knockdown in TEM8-overexpressing cells.	SIGNOR-280107
Q13451	P51608	transcriptional regulation	down-regulates quantity by repression	0.306	These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.	SIGNOR-264542
Q9Y613	P12931	phosphorylation	up-regulates activity	0.306	Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK.	SIGNOR-276612
P53350	P40763	transcriptional regulation	up-regulates quantity by expression	0.306	Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.	SIGNOR-271690
Q9Y2K6	Q13535	phosphorylation	down-regulates activity	0.306	On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization.\|USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation.	SIGNOR-278393
P09471	P49683	binding	up-regulates activity	0.306	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256973
P31269	Q8NFU7	transcriptional regulation	up-regulates quantity by expression	0.306	Furthermore, TET1 catalytic domain possessed demethylase activity in cancer cells, being able to inhibit the CpG methylation of tumor suppressor gene (TSG) promoters and reactivate their expression, such as SLIT2, ZNF382 and HOXA9.	SIGNOR-259094
Q9Y5Q3	P54821	binding	down-regulates activity	0.306	Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.	SIGNOR-221899
Q9Y446	P12931	phosphorylation	up-regulates activity	0.306	We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.	SIGNOR-273807
Q9UHF7	P43026	relocalization	up-regulates activity	0.306	Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1.	SIGNOR-251867
P08069	P43250	phosphorylation	down-regulates quantity by destabilization	0.306	GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation	SIGNOR-276412
P20929	P49841	phosphorylation	down-regulates	0.306	Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly.	SIGNOR-175659
O43293	Q13464	phosphorylation	up-regulates activity	0.306	ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.	SIGNOR-279102
O94907	P50553	transcriptional regulation	down-regulates quantity by repression	0.306	We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.	SIGNOR-245885
P05106	Q15118	phosphorylation	down-regulates activity	0.306	PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.	SIGNOR-250264
P35222	Q13882	phosphorylation	down-regulates quantity	0.305	PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.\|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.	SIGNOR-278289
A8MYZ6	Q13627	phosphorylation	down-regulates	0.305	Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity	SIGNOR-183680
Q13428	P68400	phosphorylation	up-regulates activity	0.305	Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1\|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2	SIGNOR-265086
P00748	P05121	binding	down-regulates activity	0.305	C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1).	SIGNOR-263516
Q02447	P28482	phosphorylation	up-regulates	0.305	Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.	SIGNOR-157272
P46937	Q15831	phosphorylation	down-regulates activity	0.305	LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.\|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function.	SIGNOR-280139
P09486	P15036	transcriptional regulation	up-regulates quantity by expression	0.305	Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin	SIGNOR-259874
P46527	Q14012	phosphorylation	up-regulates activity	0.305	We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;\|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia.	SIGNOR-261194
Q8NFG4	P07900	binding	up-regulates quantity by stabilization	0.305	Here we show that the stability of the tumour suppressor folliculin (FLCN) depends on the chaperone function of Hsp90.	SIGNOR-256505
P46531	Q8NFP9	binding	down-regulates activity	0.305	Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated.\|Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for neural development.	SIGNOR-266010
P06850	P10275	transcriptional regulation	down-regulates quantity by repression	0.305	A direct androgenic involvement in the expression of human corticotropin-releasing hormone\|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.	SIGNOR-268723
Q96MU7	P00519	phosphorylation	down-regulates	0.305	We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.	SIGNOR-125167
Q96Q42	P51149	binding	down-regulates activity	0.305	The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis	SIGNOR-277778
O00418	P17612	phosphorylation	up-regulates activity	0.305	EEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca(2+)/calmodulin (CaM)-independent eEF-2K activity. sites of phosphorylation were Ser-365 and Ser-499	SIGNOR-250354
P48436	Q13464	phosphorylation	up-regulates	0.305	Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation	SIGNOR-162643
P21127	Q9UQ88	phosphorylation	up-regulates	0.305	Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)	SIGNOR-169628
Q05397	Q00535	phosphorylation	up-regulates	0.305	Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.	SIGNOR-86223
P19634	O00141	phosphorylation	up-regulates activity	0.304	Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].\|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.	SIGNOR-280123
Q13153	Q16584	phosphorylation	up-regulates activity	0.304	Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.\|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.	SIGNOR-279418
Q16584	O95819	phosphorylation	up-regulates activity	0.304	The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling.	SIGNOR-277571
P06213	Q12913	dephosphorylation	down-regulates	0.304	Dephosphorylation of autophosphorylated insulin and epidermal-growth-factor receptors by two major subtypes of protein-tyrosine-phosphatase from human placenta.	SIGNOR-21295
P04626	P43378	dephosphorylation	down-regulates activity	0.304	Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.\|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.	SIGNOR-277170
Q13568	O43353	phosphorylation	up-regulates	0.304	Activation of interferon regulatory factor 5 by site specific phosphorylation. Phosphorylation of carboxyl serines 451 and 462 appear the primary trigger of irf5 function in nuclear accumulation, transcription, and apoptosis. Rip2 activation of the irf5 aspartic acid substitutions showed a similar positive effect of s451d and s462d function in this assay	SIGNOR-196524
Q969T9	P07947	phosphorylation	up-regulates activity	0.304	Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.	SIGNOR-273582
P38936	O15119	transcriptional regulation	down-regulates quantity by repression	0.304	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249602
O43597	Q13627	phosphorylation	down-regulates	0.304	We identify dyrk1a as one of the protein kinases of sprouty2. We show that dyrk1a interacts with and regulates the phosphorylation status of sprouty2. Moreover, we identify thr75 on sprouty2 as a dyrk1a phosphorylation site in vitro and in vivo.	SIGNOR-179828
O14965	Q14CS0	binding	down-regulates activity	0.304	The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.\|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts	SIGNOR-265042
Q15672	P28482	phosphorylation	up-regulates	0.304	We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells.	SIGNOR-173401
P43004	Q96PU5	ubiquitination	down-regulates quantity	0.304	Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).\|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD.	SIGNOR-278706
O14686	P23759	binding	up-regulates	0.304	Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.	SIGNOR-198629
Q05195	P23443	phosphorylation	down-regulates	0.304	Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway, which in turn promotes the transcriptional activity of myc.	SIGNOR-178590
Q16584	Q16539	phosphorylation	down-regulates	0.304	Jnk and p38 mapk activation have antagonistic effects in many cases. From a mechanicistic point of view, the p38 mapk pathway can negatively regulate jnk activity at the level of map3ks, either by phosphorylating mlk3 or the tak1 regulatory subunit tab2	SIGNOR-166605
O95997	P27361	phosphorylation	up-regulates	0.304	Pttg is phosphorylated in vitro on ser(162) by map kinase and this phosphorylation site plays an essential role in pttg transactivation function.	SIGNOR-79519
Q92858	Q7Z6Z7	ubiquitination	down-regulates quantity	0.304	Huwe1 ubiquitinates and degrades Atoh1, and robustly affects development of GNPs that express this transcription factor [ xref ].\|This provides further evidence that phosphorylation of Atoh1 affects Huwe1-mediated degradation, and demonstrates that Huwe1 inhibits Atoh1 to affect cellular differentiation in multiple cell types.	SIGNOR-278693
O43561	P27361	phosphorylation	down-regulates	0.304	Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.	SIGNOR-125770
Q92878	Q08999	binding	up-regulates activity	0.304	We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.	SIGNOR-265029
P54646	Q8IYT8	phosphorylation	down-regulates	0.304	We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I	SIGNOR-173089
Q99459	O96017	phosphorylation	down-regulates activity	0.304	Remarkably, however, the activation of the DDC triggers a Rad53-dependent phosphorylation of Cdc5 that inhibits the polo-like kinase, thus favoring Cdh1 activity and subsequently also restraining spindle elongation and anaphase progression [34,54] (Figure 1).	SIGNOR-279694
P53675	Q676U5	binding	up-regulates	0.304	Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors	SIGNOR-166705
P17861	P28066	binding	down-regulates quantity by destabilization	0.304	We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.	SIGNOR-239213
P29375	P31749	phosphorylation	up-regulates activity	0.303	We immunoprecipitated ectopically expressed wild-type KDM5A or KDM5Amut5A and performed an in vitro kinase assay using recombinant AKT1 in the presence or absence of AKT inhibition.Wild-type KDM5A is phosphorylated by AKT1 and this modification is sensitive to AKT inhibition, whereas KDM5Amut5A is not phosphorylated in the presence of AKT1 (Figure 3C).These results suggest that AKT-mediated KDM5A phosphorylation enhances KDM5A promoter recruitment.	SIGNOR-274062
Q13153	Q8WY54	dephosphorylation	down-regulates activity	0.303	The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family\|POPX Can Dephosphorylate and Downregulate PAK\| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.	SIGNOR-248761
Q9H0H5	P67775	dephosphorylation	down-regulates	0.303	We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.	SIGNOR-160398
Q5JVS0	Q04759	phosphorylation	down-regulates activity	0.303	We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. \| This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. \| Ki-1/57 Exits the Nucleus upon PMA Activation	SIGNOR-249256
Q01860	Q9UNE7	ubiquitination	down-regulates quantity by destabilization	0.303	CHIP overexpression decreased OCT4 stability through proteasomal degradation.\|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.\|These data suggest that CHIP induces OCT4 ubiquitination and degradation.	SIGNOR-278562
Q86VP3	Q13490	polyubiquitination	down-regulates quantity by destabilization	0.303	Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay.	SIGNOR-272851
P01106	P62633	transcriptional regulation	down-regulates quantity by repression	0.303	These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex.	SIGNOR-261571
P04004	P05771	phosphorylation	up-regulates quantity by stabilization	0.303	Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.	SIGNOR-248963
Q9NZN5	Q05397	phosphorylation	up-regulates activity	0.303	These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa.	SIGNOR-279310
P45983	Q96KB5	phosphorylation	up-regulates activity	0.303	Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.\|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.	SIGNOR-280061
Q96PH1	P00519	phosphorylation	up-regulates activity	0.303	As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.\|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites.	SIGNOR-280170
Q96T88	P24941	phosphorylation	down-regulates quantity by destabilization	0.303	UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant	SIGNOR-277192
Q9UJU2	P68400	phosphorylation	up-regulates	0.303	Here, we identify ck1 and ck2 as major kinases that directly bind to and phosphorylate lef-1 inducing distinct, kinase-specific changes in the lef-1/dna complex.CK1-dependent phosphorylation inhibits, whereas ck2 activates lef-1/beta-catenin transcriptional activity in reporter gene assays.	SIGNOR-23958
Q06710	Q9GZV5	binding	up-regulates	0.303	Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.	SIGNOR-182253
P83916	P68400	phosphorylation	down-regulates	0.303	Two recent papers suggest that hp1 recruitment to damage sites, rather than its rapid mobilization, is the predominant behaviour exhibited by this protein. Our findings reconcile recent findings in a new model, wherein rapid hp1beta mobilization from dsbs is mediated by its phosphorylation on thr51 by ck2	SIGNOR-187450
P55957	Q9Y6C9	relocalization	up-regulates	0.303	Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria	SIGNOR-165081
P17861	P60900	binding	down-regulates quantity by destabilization	0.303	We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.	SIGNOR-239039
P12821	P68400	phosphorylation	up-regulates activity	0.303	CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation.\|These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels.	SIGNOR-264425
P55040	P63104	binding	up-regulates quantity by stabilization	0.303	In order to address whether Gem binds specific isoforms of 14-3-3, we determined the coassociation of Gem and 14-3-3 in the neuroblastoma cell line SY5Y. 14-3-3ζ, -γ, -τ, and -β were observed to bind to Gem. 14-3-3-bound Gem has a twofold-longer half-life than nonbound Gem (Fig. (Fig.6).6). A similar increase in protein stability following 14-3-3 binding has been described for the Wee1 kinase	SIGNOR-261715
Q15717	P49137	phosphorylation	up-regulates	0.303	Mk2 and mk3 participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating the are-binding proteins ttp and hur, and by regulating eef2k	SIGNOR-166622
P46531	Q9BWU1	phosphorylation	down-regulates quantity by destabilization	0.302	Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues	SIGNOR-273135
P12036	P49841	phosphorylation	down-regulates	0.302	Gsk3beta was shown to phosphorylate at ser-493 in vitro by phosphopeptide mapping and site-directed mutagenesis, and in vivo in hek293 cells. The role of ser-493 phosphorylation is also a question to be addressed in the future. Because the e-segment appears to be involved in filament formation (27, 42), phosphorylation in that region may also play a regulatory role in filament formation. Secondary structure prediction suggests that phosphorylation of ser-493 in combination with following the pro residue interrupts _-helix of the e-segment	SIGNOR-90668
P22888	P10588	transcriptional regulation	down-regulates quantity by repression	0.302	Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.	SIGNOR-266216
Q8N726	Q9HCX3	transcriptional regulation	down-regulates quantity by repression	0.302	Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.	SIGNOR-266098
P98066	P17676	transcriptional regulation	up-regulates quantity by expression	0.302	In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells.	SIGNOR-254055
O43248	O15550	transcriptional regulation	up-regulates quantity by expression	0.302	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260026
P30307	P68400	phosphorylation	down-regulates	0.302	Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm	SIGNOR-123713
P52735	Q16620	phosphorylation	up-regulates activity	0.302	Finally, the TrkB kinase dependent increase in P-Y172 Vav2 was largely independent of the Vav2 SH2 domain (XREF_FIG, right), which was previously shown to be important for activation by Eph receptors.\|These findings reveal a strong kinase independent binding mechanism between Vav and TrkB in cells, and suggest that activation of TrkB kinase activity stimulates Vav2 tyrosine phosphorylation and GEF activity.	SIGNOR-280050
Q8N8S7	Q13976	phosphorylation	down-regulates activity	0.302	Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction.	SIGNOR-268288
P19838	P50591	post transcriptional regulation	up-regulates quantity by expression	0.302	Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.	SIGNOR-277936
Q2M1Z3	P49841	phosphorylation	up-regulates activity	0.302	We show that GSK-3alpha and -beta interact with CdGAP in mammalian cells. We also demonstrate that GSK-3 phosphorylates CdGAP both in vitro and in vivo on Thr-776, which we have previously shown to be an ERK 1/2 phosphorylation site involved in CdGAP regulation.	SIGNOR-262879

Q86VB7

P67870

0

phosphorylation

up-regulates activity

0.307

Interaction of CD163 with the regulatory subunit of casein kinase II (CKII) and dependence of CD163 signaling on CKII and protein kinase C. | Inhibition studies using specific kinase inhibitors reveal that both CKII and PKC are involved in the CD163 signaling mechanism resulting in the secretion of proinflammatory cytokines.

SIGNOR-251056

P52945

P13010

0

binding

down-regulates quantity by destabilization

0.307

The interaction of PDX-1 with Ku subunits and its phosphorylation on threonine 11 by the DNA-PK appear to be implicated in its degradation by the proteosome.

SIGNOR-225537

P05549

P54646

0

phosphorylation

up-regulates activity

0.307

Inhibition of AMPKalpha2 with either siRNA or compound C significantly suppressed the AngII- or nicotine enhanced AP-2alpha activity and the binding of AP-2alpha to DNA.|We report that nicotine, a major component of cigarette smoke, activates AMPK in VSMCs and that AMPKalpha2 phosphorylates AP-2alpha at serine 219 resulting in aberrant expression of MMP2 and consequent AAA formation.

SIGNOR-279648

P00441

P14174

0

relocalization

down-regulates quantity by destabilization

0.307

Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein

SIGNOR-262797

Q16625

P05129

0

phosphorylation

up-regulates activity

0.307

Protein kinase C regulates the phosphorylation and cellular localization of occludin. Ser(338) of occludin was identified as an in vitro protein kinase C phosphorylation site using peptide mass fingerprint analysis and electrospray ionization tandem mass spectroscopy. Both the phosphorylation of occludin and its incorporation into tight junctions induced by calcium switch were markedly inhibited by the PKC inhibitor GF-109203X.

SIGNOR-249107

O14813

P17612

0

phosphorylation

down-regulates

0.307

Phox2a becomes phosphorylated by protein kinase a (pka) on ser153, which prevents association of phox2a with dna and terminates p27(kip1) transcription.

SIGNOR-186462

Q9H2X6

P12931

0

phosphorylation

up-regulates activity

0.307

Using mass spectrometry we identified 9 Src-mediated Tyr-phosphorylation sites within HIPK2, 5 of them positioned in the kinase domain.|We demonstrate that ectopic expression of Src increases the half-life of HIPK2 by interfering with Siah-1-mediated HIPK2 degradation.

SIGNOR-278989

O14713

Q9UQM7

0

phosphorylation

up-regulates activity

0.307

The point mutation T38D localized within the optimal CaMKII recognition motif of ICAP-1alpha results in a strong defect in cell spreading which cannot be overcome by the inhibition of the endogenous CaMKII. This fact strongly suggests that the phosphorylation of Threonine 38 by CaMKII modulates the alpha5beta1 integrin function. Conversely, the mutation T38A produces an analog of ICAP-1alpha that cannot be phosphorylated and that stimulates cell spreading on fibronectin to a similar extent when CaMKII is inhibited.

SIGNOR-250632

Q99538

Q9Y4K3

0

polyubiquitination

up-regulates quantity by stabilization

0.307

We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6/HSP90α complex formation.

SIGNOR-272853

P61925

P00533

0

phosphorylation

up-regulates

0.307

The difference in inhibitory potency between pki_ and pki_ has been attributed to the absence of a tyrosine residue (tyr7) in pki_ that is present in the nh2-terminal region of pki_. This suggests that the absence of a single amino acid residue can result in variations in how the catalytic subunit of camp-dependent protein kinase interacts with pki which ultimately can result in alterations in pki inhibitory potency.

SIGNOR-22455

P05549

P68400

0

phosphorylation

up-regulates

0.307

Ck2 phosphorylates ap-2_ and increases its transcriptional activity

SIGNOR-175130

Q14847

P17612

0

phosphorylation

down-regulates activity

0.306

Lasp-1 binds to non-muscle filamentous (F) actin in vitro in a phosphorylation-dependent manner. Phosphorylation of recombinant lasp-1 with recombinant PKA increased the Kd and decreased the Bmax for lasp-1 binding to F-actin. PKA-dependent phosphorylation sites in rabbit lasp-1 to S99 and S146

SIGNOR-250074

Q13469

Q00987

0

ubiquitination

down-regulates quantity

0.306

MDM2 negatively regulates NFATc2 and T cell activation.|The E3 ubiquitin ligase MDM2 is known to induce NFATc2 ubiquitination in a breast cancer cell line 24.

SIGNOR-278657

P01111

P49842

0

phosphorylation

up-regulates activity

0.306

STK19 Phosphorylates NRAS Protein at Serine 89|STK19 phosphorylates NRAS to enhance its binding to its downstream effectors and promotes oncogenic NRAS-mediated melanocyte malignant transformation.|

SIGNOR-264566

Q99717

Q13464

0

phosphorylation

up-regulates activity

0.306

The results showed that SMAD5 was directly phosphorylated at Ser463/465 by ROCK1 (Fig.\u00a04g).|These data indicated that the activation of SMAD5 induced by TEM8 was mediated directly by the RhoC/ROCK1 pathway.To evaluate the effect of SMAD5 on the cellular functions of TEM8, SMAD5 was knockdown in TEM8-overexpressing cells.

SIGNOR-280107

Q13451

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.306

These results are compatible with the hypothesis that MeCP2 associates with the Sgk and Fkbp5 promoters and has a repressive effect that is over-ridden by elevated glucocorticoids in response to stress.

SIGNOR-264542

Q9Y613

P12931

0

phosphorylation

up-regulates activity

0.306

Our results show that only Src can efficiently phosphorylate FHOD1 at Y99 to enable the downstream activation by ROCK.

SIGNOR-276612

P53350

P40763

0

transcriptional regulation

up-regulates quantity by expression

0.306

Stat3 directly activated transcription of PLK1 in esophageal cancer cells and mouse embryonic fibroblast cell NIH3T3.

SIGNOR-271690

Q9Y2K6

Q13535

0

phosphorylation

down-regulates activity

0.306

On the other hand, USP20 is phosphorylated by ATR, which disrupts the interaction between USP20 and HERC2, resulting in USP20 stabilization.|USP20 phosphorylation by ATR is important for its stabilization and checkpoint activation.

SIGNOR-278393

P09471

P49683

0

binding

up-regulates activity

0.306

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256973

P31269

Q8NFU7

0

transcriptional regulation

up-regulates quantity by expression

0.306

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

SIGNOR-259094

Q9Y5Q3

P54821

0

binding

down-regulates activity

0.306

Hoxd12 and MHox, that interact with v-/c-Maf, using the phage display method. The Hox proteins also could associate with the other Maf protein family members, MafB, MafK, MafF, and MafG, but not with Jun and Fos. The Hox proteins negatively regulated the DNA binding, transactivation and cell-transforming abilities of Maf.

SIGNOR-221899

Q9Y446

P12931

0

phosphorylation

up-regulates activity

0.306

We have discovered that reactive oxygen species (ROS) trigger the c-Src kinase-mediated tyrosine (Tyr)-195 phosphorylation of PKP3. This modification is associated with a change in the subcellular distribution of the protein. Specifically, PKP3 bearing phospho-Tyr-195 is released from the desmosomes, suggesting that phospho-Tyr-195 is relevant for the control of desmosome disassembly and function, at least in cells exposed to ROS.

SIGNOR-273807

Q9UHF7

P43026

0

relocalization

up-regulates activity

0.306

Treatment of cells with Gdf5 enhanced Trps1 protein levels and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a dose-dependent manner. Nuclear translocation of Trps1 was also induced by Gdf5. These effects were blocked by a dominant negative form of activin-linked kinase 6 (dn-Alk6) and by SB203580, an inhibitor of the p38 MAPK pathway. Conversely, Gdf5 expression was suppressed by the over-expression of Trps1.

SIGNOR-251867

P08069

P43250

0

phosphorylation

down-regulates quantity by destabilization

0.306

GRK2 and GRK6 coimmunoprecipitate with IGF-1R and increase IGF-1R serine phosphorylation, promoting β-arrestin1 association. Using immunoprecipitation, confocal microscopy, and FRET analysis, we demonstrated β-arrestin/IGF-1R association to be transient for GRK2 and stable for GRK6. Using bioinformatic studies we identified serines 1248 and 1291 as the major serine phosphorylation sites of the IGF-1R. Targeted mutation of S1248 recapitulates GRK2 modulation, whereas S1291 mutation resembles GRK6 effects on IGF-1R signaling/degradation

SIGNOR-276412

P20929

P49841

0

phosphorylation

down-regulates

0.306

Gsk3b is able to phosphorylate nebulin at two ser sites in the c-terminal region of nebulin localized to the z-disk, thus preventing the interaction of nebulin with neuronal wiscott-aldrich syndrome protein (nwasp), a ubiquitously expressed member of the wasp family, which is involved in actin assembly.

SIGNOR-175659

O43293

Q13464

0

phosphorylation

up-regulates activity

0.306

ROCK1 phosphorylates and activates ZIPK suggesting that at least some of these physiological functions may require both enzymes.

SIGNOR-279102

O94907

P50553

0

transcriptional regulation

down-regulates quantity by repression

0.306

We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1.

SIGNOR-245885

P05106

Q15118

0

phosphorylation

down-regulates activity

0.306

PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.

SIGNOR-250264

P35222

Q13882

0

phosphorylation

down-regulates quantity

0.305

PTK6 directly phosphorylates beta-catenin on Tyr64, Tyr142, Tyr331 and/or Tyr333, with the predominant site being Tyr64.|The ability of PTK6 to negatively regulate beta-catenin and TCF transcription by modulating levels of TCF4 and TLE and Groucho could contribute to its growth-inhibitory activities in vivo.

SIGNOR-278289

A8MYZ6

Q13627

0

phosphorylation

down-regulates

0.305

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

SIGNOR-183680

Q13428

P68400

0

phosphorylation

up-regulates activity

0.305

Phosphorylated Thr 210 in Treacle is the major interaction site for NBS1|A purified GST fragment of this region was efficiently phosphorylated by CK2 in vitro (Supplementary Fig. 4; T-2) and this fragment pulled down the MRN complex from Hela nuclear extracts only when previously phosphorylated by CK2

SIGNOR-265086

P00748

P05121

0

binding

down-regulates activity

0.305

C1INH is a serine protease inhibitor (serpin) that acts on both the complement pathway and the contact system and is the main inhibitor of the contact system by targeting both FXIIa and PK 9. Additionally, FXIIa can be inhibited by α1‐antitrypsin and plasminogen activator inhibitor‐1 (PAI‐1).

SIGNOR-263516

Q02447

P28482

0

phosphorylation

up-regulates

0.305

Here, we show that sp3, which, as sp1, belongs to the gc-rich binding transcription factor family, is also phosphorylated by erk in vitro on serine 73. in the inducible cell lines, expression of wild-type form of sp3 increases vegf production whereas the s73a form has a reduced potential reflecting its lower transcriptional activity.

SIGNOR-157272

P46937

Q15831

0

phosphorylation

down-regulates activity

0.305

LKB1 induces phosphorylation of Yap, leading to Yap nuclear exclusion and ultimately its degradation.|These data indicated that LKB1 expression inhibits Yes-associated protein transcriptional function.

SIGNOR-280139

P09486

P15036

0

transcriptional regulation

up-regulates quantity by expression

0.305

Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin

SIGNOR-259874

P46527

Q14012

0

phosphorylation

up-regulates activity

0.305

We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia.

SIGNOR-261194

Q8NFG4

P07900

0

binding

up-regulates quantity by stabilization

0.305

Here we show that the stability of the tumour suppressor folliculin (FLCN) depends on the chaperone function of Hsp90.

SIGNOR-256505

P46531

Q8NFP9

0

binding

down-regulates activity

0.305

Yeast two-hybrid identified the Notch1 intracellular domain as a physical interactor of the PBW domain and a role for NBEA as a negative regulator in Notch-mediated transcription was demonstrated.|Defining novel interaction partners of conserved NBEA domain modules identified a role for NBEA as transcriptional regulator in the nucleus. The physical interaction of NBEA with NOTCH1 is most relevant for ASD pathogenesis because NOTCH signaling is essential for neural development.

SIGNOR-266010

P06850

P10275

0

transcriptional regulation

down-regulates quantity by repression

0.305

A direct androgenic involvement in the expression of human corticotropin-releasing hormone|A potential androgen-responsive element (ARE) in the human CRH promoter was subsequently analyzed with bandshifts and cotransfections in neuroblastoma cells. In the presence of testosterone, recombinant human AR bound specifically to the CRH-ARE.

SIGNOR-268723

Q96MU7

P00519

0

phosphorylation

down-regulates

0.305

We show that yt521-b is tyrosine phosphorylated by c-abl in the nucleus.We propose that tyrosine phosphorylation causes sequestration of YT521-B in an insoluble nuclear form, which abolishes the ability of YT521-B to change alternative splice sites.

SIGNOR-125167

Q96Q42

P51149

0

binding

down-regulates activity

0.305

The absence of active Rab7 prolongs ALS2presence and Rab5 activation on macropinosomes, indicating that activeRab7 is necessary for Rab5 inactivation through ALS2 dissociation and playskey roles in the Rab switch on macropinosomes. Taken together, active Rab7is necessary for Rab5 down-regulation through ALS2dissociation, thereby acting as a central component inthe Rab5-to-Rab7 switch in macropinocytosis

SIGNOR-277778

O00418

P17612

0

phosphorylation

up-regulates activity

0.305

EEF-2K can be phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and that this induces significant Ca(2+)/calmodulin (CaM)-independent eEF-2K activity. sites of phosphorylation were Ser-365 and Ser-499

SIGNOR-250354

P48436

Q13464

0

phosphorylation

up-regulates

0.305

Rho kinase-dependent activation of sox9 in chondrocytes. In vitro, rock directly phosphorylated sox9 at ser(181), and the overexpression of rock or the activation of the rhoa pathway in sw1353 chondrosarcoma cells increased sox9(ser181) phosphorylation

SIGNOR-162643

P21127

Q9UQ88

0

phosphorylation

up-regulates

0.305

Overall, our data indicated that thr-370 is responsible for the autophosphorylation, dimerization, and kinase activity of cdk11(p58)

SIGNOR-169628

Q05397

Q00535

0

phosphorylation

up-regulates

0.305

Here, we show that fak phosphorylation by cdk5 at s732 is important for microtubule organization, nuclear movement, and neuronal migration. In cultured neurons, s732-phosphorylated fak is enriched along a centrosome-associated microtubule fork that abuts the nucleus. Overexpression of the nonphosphorylatable mutant fak s732a results in disorganization of the microtubule fork and impairment of nuclear movement in vitro, and neuronal positioning defects in vivo.

SIGNOR-86223

P19634

O00141

0

phosphorylation

up-regulates activity

0.304

Phosphorylation of NHE1 Ser 703 by SGK1 is essential for the binding of 14-3-3 protein to NHE1 , ] which, in turn, is critical in the activation of this Na + / H + exchanger , ].|These data suggest that endothelial SGK1 activates NHE1 in response to MG treatment.

SIGNOR-280123

Q13153

Q16584

0

phosphorylation

up-regulates activity

0.304

Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.

SIGNOR-279418

Q16584

O95819

0

phosphorylation

up-regulates activity

0.304

The MAP4K4 and MLK3 associates with each other, and MAP4K4 phosphorylates MLK3 on Thr738 and increases MLK3 kinase activity and downstream signaling.

SIGNOR-277571

P06213

Q12913

0

dephosphorylation

down-regulates

0.304

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

SIGNOR-21295

P04626

P43378

0

dephosphorylation

down-regulates activity

0.304

Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.

SIGNOR-277170

Q13568

O43353

0

phosphorylation

up-regulates

0.304

Activation of interferon regulatory factor 5 by site specific phosphorylation. Phosphorylation of carboxyl serines 451 and 462 appear the primary trigger of irf5 function in nuclear accumulation, transcription, and apoptosis. Rip2 activation of the irf5 aspartic acid substitutions showed a similar positive effect of s451d and s462d function in this assay

SIGNOR-196524

Q969T9

P07947

0

phosphorylation

up-regulates activity

0.304

Using dominant-negative, constitutively active mutants, RNAi, and pharmacological studies, we demonstrated that phosphorylation of WBP2 at Tyr192 and Tyr231 could be regulated by c-Src and c-Yes kinases.We further showed that abrogating WBP2 phosphorylation impaired >60% of ERα reporter activity, putatively by blocking nuclear entry of WBP2 and its interaction with ERα.

SIGNOR-273582

P38936

O15119

0

transcriptional regulation

down-regulates quantity by repression

0.304

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249602

O43597

Q13627

0

phosphorylation

down-regulates

0.304

We identify dyrk1a as one of the protein kinases of sprouty2. We show that dyrk1a interacts with and regulates the phosphorylation status of sprouty2. Moreover, we identify thr75 on sprouty2 as a dyrk1a phosphorylation site in vitro and in vivo.

SIGNOR-179828

O14965

Q14CS0

0

binding

down-regulates activity

0.304

The UBXN-2/p37/p47 adaptors of CDC-48/p97 regulate mitosis by limiting the centrosomal recruitment of Aurora A.|We found that UBXN-2 and CDC-48 coimmunoprecipitated with AIR-1 from embryonic extracts

SIGNOR-265042

Q15672

P28482

0

phosphorylation

up-regulates

0.304

We identified the serine 68 (s68) as a major phosphorylation site of twist1 by mass spectrometry and with specific antibodies. This s68 is phosphorylated by p38, jnk and erk1/2 in vitro, and its phosphorylation levels positively correlate with twist1 protein levels in hek293 and breast cancer cells.

SIGNOR-173401

P43004

Q96PU5

0

ubiquitination

down-regulates quantity

0.304

Our results confirm that Nedd4-2 knockdown in MPTP treated mice increased GLT-1 expression at the membrane protein level (XREF_FIG; P < 0.01).|These results suggest that Nedd4-2 mediates the ubiquitination of both GLT-1 and GLAST in the midbrain in MPTP treated mice, and Nedd4-2 maybe a potential target in regulating glutamate transporters in PD.

SIGNOR-278706

O14686

P23759

0

binding

up-regulates

0.304

Carm1 specifically methylates multiple arginines in the n-terminus of pax7. Methylated pax7 directly binds the c-terminal cleavage forms of the trithorax proteins mll1/2 resulting in the recruitment of the ash2l:mll1/2:wdr5:rbbp5 histone h3k4 methyltransferase complex to regulatory enhancers and the proximal promoter of myf5.

SIGNOR-198629

Q05195

P23443

0

phosphorylation

down-regulates

0.304

Both rsk and s6k phosphorylate serine 145 of mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of mad1 accelerates the ubiquitination and degradation of mad1 through the 26s proteasome pathway, which in turn promotes the transcriptional activity of myc.

SIGNOR-178590

Q16584

Q16539

0

phosphorylation

down-regulates

0.304

Jnk and p38 mapk activation have antagonistic effects in many cases. From a mechanicistic point of view, the p38 mapk pathway can negatively regulate jnk activity at the level of map3ks, either by phosphorylating mlk3 or the tak1 regulatory subunit tab2

SIGNOR-166605

O95997

P27361

0

phosphorylation

up-regulates

0.304

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

SIGNOR-79519

Q92858

Q7Z6Z7

0

ubiquitination

down-regulates quantity

0.304

Huwe1 ubiquitinates and degrades Atoh1, and robustly affects development of GNPs that express this transcription factor [ xref ].|This provides further evidence that phosphorylation of Atoh1 affects Huwe1-mediated degradation, and demonstrates that Huwe1 inhibits Atoh1 to affect cellular differentiation in multiple cell types.

SIGNOR-278693

O43561

P27361

0

phosphorylation

down-regulates

0.304

Lat, an adapter protein essential for t-cell signaling, is phosphorylated at its thr 155 by erk in response to t-cell receptor stimulation. Thr 155 phosphorylation reduces the ability of lat to recruit plcgamma1 and slp76, leading to attenuation of subsequent downstream events such as [ca2+]i mobilization and activation of the erk pathway.

SIGNOR-125770

Q92878

Q08999

0

binding

up-regulates activity

0.304

We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.

SIGNOR-265029

P54646

Q8IYT8

0

phosphorylation

down-regulates

0.304

We could prove that ulk1-mediated phosphorylation of ampk reduced its level of phosphorylation at t172 of the _-subunit and hence interferes with its catalytic activity. I

SIGNOR-173089

Q99459

O96017

0

phosphorylation

down-regulates activity

0.304

Remarkably, however, the activation of the DDC triggers a Rad53-dependent phosphorylation of Cdc5 that inhibits the polo-like kinase, thus favoring Cdh1 activity and subsequently also restraining spindle elongation and anaphase progression [34,54] (Figure 1).

SIGNOR-279694

P53675

Q676U5

0

binding

up-regulates

0.304

Clathrin heavy-chain interacts with atg16l1, and is involved in the formation of atg16l1-positive early autophagosome precursors

SIGNOR-166705

P17861

P28066

0

binding

down-regulates quantity by destabilization

0.304

We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.

SIGNOR-239213

P29375

P31749

0

phosphorylation

up-regulates activity

0.303

We immunoprecipitated ectopically expressed wild-type KDM5A or KDM5Amut5A and performed an in vitro kinase assay using recombinant AKT1 in the presence or absence of AKT inhibition.Wild-type KDM5A is phosphorylated by AKT1 and this modification is sensitive to AKT inhibition, whereas KDM5Amut5A is not phosphorylated in the presence of AKT1 (Figure 3C).These results suggest that AKT-mediated KDM5A phosphorylation enhances KDM5A promoter recruitment.

SIGNOR-274062

Q13153

Q8WY54

0

dephosphorylation

down-regulates activity

0.303

The p21-activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family|POPX Can Dephosphorylate and Downregulate PAK| To confirm that POPX2 acts on αPAK phospho-Thr422, a key regulator of activity in the kinase activation loop [9], we used phospho-specific antibodies against αPAK P-Thr422 (Figure 3B, lower panel), which proved to be an excellent substrate for POPX2. Similarly, complete loss of αPAK P-Ser57 with 0.2 μg POPX2 contrasts with the slight loss observed with 1.5 μg PP1. On the basis of these results, we suggest PAK is a substrate of POPX.

SIGNOR-248761

Q9H0H5

P67775

0

dephosphorylation

down-regulates

0.303

We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.

SIGNOR-160398

Q5JVS0

Q04759

0

phosphorylation

down-regulates activity

0.303

We found a strong phosphorylation of Ki-1/57 by PKCalphabeta, PKCdelta, PKClambda/zeta, and especially by PKCsigma, however not by PKCmi. These data show that Ki-1/57 can serve in principal as a substrate for a wide variety of different PKC isoforms but also that its phosphorylation is strongest with PKCsigma. | This suggests that the two threonine residues present in this fragment (Thr354 and Thr375) might be the main target residues for phosphorylation by PKC in vitro. | Ki-1/57 Exits the Nucleus upon PMA Activation

SIGNOR-249256

Q01860

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.303

CHIP overexpression decreased OCT4 stability through proteasomal degradation.|CHIP E3 ligase ubiquitinates OCT4 at lysine 284.|These data suggest that CHIP induces OCT4 ubiquitination and degradation.

SIGNOR-278562

Q86VP3

Q13490

0

polyubiquitination

down-regulates quantity by destabilization

0.303

Under basal conditions, PACS-2 underwent K48-linked poly-ubiquitination, resulting in PACS-2 proteasomal degradation. Biochemical assays showed cIAP-1 and cIAP-2 interacted with PACS-2 in vitro and co-immunoprecipitation studies demonstrated that the two cIAPs bound PACS-2 in vivo. More importantly, both cIAP-1 and cIAP-2 directly mediated PACS-2 ubiquitination in a cell-free assay.

SIGNOR-272851

P01106

P62633

0

transcriptional regulation

down-regulates quantity by repression

0.303

These data verified that the binding of CNBP with c-myc promoter G-quadruplex can indeed down-regulate its associated gene expression for a certain period of time. This result with human CNBP is somehow consistent with previous reports that c-myc G-quadruplex serves as a silencer of c-myc transcription [7] and CNBP promotes the formation of c-myc G-quadruplex.

SIGNOR-261571

P04004

P05771

0

phosphorylation

up-regulates quantity by stabilization

0.303

Phosphorylation of vitronectin on Ser362 by protein kinase C attenuates its cleavage by plasmin.

SIGNOR-248963

Q9NZN5

Q05397

0

phosphorylation

up-regulates activity

0.303

These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa.

SIGNOR-279310

P45983

Q96KB5

0

phosphorylation

up-regulates activity

0.303

Taken together, these findings showed that TOPK positively modulated UVB-induced JNK1 activity and played a pivotal role in JNK1-mediated cell transformation induced by H-Ras.|We showed that TOPK associated with and phosphorylated JNK1 following UVB irradiation in vitro or in vivo.

SIGNOR-280061

Q96PH1

P00519

0

phosphorylation

up-regulates activity

0.303

As shown in Fig. xref and c, c-Abl-phosphorylated NOX5 was mostly inhibited when c-Abl plasmid co-transfected with NOX5 Y476/Y478F mutant, then the NOX5 Y487F mutant, but not with NOX5 Y519F mutant.|Collectively, these results indicate that Pyk2 may act as a scaffolding protein for c-Abl stimulation of NOX5 activity in Pyk2 and NOX5 complex, and c-Abl-enhanced NOX5 activity is mainly dependent on phosphorylation of NOX5 Tyr 476/478 sites.

SIGNOR-280170

Q96T88

P24941

0

phosphorylation

down-regulates quantity by destabilization

0.303

UHRF1 is phosphorylated by CDK2/cyclin A. In vitro kinase assay was performed with CDK2/cyclin A using recombinant wild-type UHRF1 or UHRF1-S674A mutant

SIGNOR-277192

Q9UJU2

P68400

0

phosphorylation

up-regulates

0.303

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

SIGNOR-23958

Q06710

Q9GZV5

0

binding

up-regulates

0.303

Taz is a coactivator for pax8 and ttf-1, two transcription factors involved in thyroid differentiation. / we show that this interaction leads to a significant enhancement of the transcriptional activity of pax8 and ttf-1 on the thyroglobulin promoter thus suggesting a role of taz in the control of genes involved in thyroid development and differentiation.

SIGNOR-182253

P83916

P68400

0

phosphorylation

down-regulates

0.303

Two recent papers suggest that hp1 recruitment to damage sites, rather than its rapid mobilization, is the predominant behaviour exhibited by this protein. Our findings reconcile recent findings in a new model, wherein rapid hp1beta mobilization from dsbs is mediated by its phosphorylation on thr51 by ck2

SIGNOR-187450

P55957

Q9Y6C9

0

relocalization

up-regulates

0.303

Mtch2/mimp (mitochondrial carrier homologue 2/met-induced mitochondrial protein), a novel truncated bid (tbid)-interacting protein, is a surface-exposed outer mitochondrial membrane protein that facilitates the recruitment of tbid to mitochondria

SIGNOR-165081

P17861

P60900

0

binding

down-regulates quantity by destabilization

0.303

We saw preferential binding of XBP-1u to subunits _5, _6 and _7.2. We demonstrate that XBP-1u undergoes efficient degradation in vitro by 20S proteasomes in the absence of ubiquitination.

SIGNOR-239039

P12821

P68400

0

phosphorylation

up-regulates activity

0.303

CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation.|These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels.

SIGNOR-264425

P55040

P63104

0

binding

up-regulates quantity by stabilization

0.303

In order to address whether Gem binds specific isoforms of 14-3-3, we determined the coassociation of Gem and 14-3-3 in the neuroblastoma cell line SY5Y. 14-3-3ζ, -γ, -τ, and -β were observed to bind to Gem. 14-3-3-bound Gem has a twofold-longer half-life than nonbound Gem (Fig. (Fig.6).6). A similar increase in protein stability following 14-3-3 binding has been described for the Wee1 kinase

SIGNOR-261715

Q15717

P49137

0

phosphorylation

up-regulates

0.303

Mk2 and mk3 participate in the control of gene expression mostly at the post-transcriptional level, by phosphorylating the are-binding proteins ttp and hur, and by regulating eef2k

SIGNOR-166622

P46531

Q9BWU1

0

phosphorylation

down-regulates quantity by destabilization

0.302

Mapping of cyclin C-dependent phosphosites on ICN1, using mass spectrometry revealed that several of them are located within the PEST-domain of Notch1, which controls ICN1 degradation38,39 (Fig. 5g and Supplementary Table 1). Three of them (T2512, S2514 and S2517) are localized within the consensus motif, “Cdc4 phosphodegron”, which is shared by most substrates of Fbw7 (Cdc4) ubiquitin ligase38. Two of these residues (S2514 and S2517) were previously shown by Fryer et al.20 to be phosphorylated by cyclin C-CDK8 in vitro, and all three were shown to play a role in controlling ICN1 stability via Fbw740. We verified that cyclin C-CDK8, C-CDK19 and C-CDK3 phosphorylate ICN1 on these three residues

SIGNOR-273135

P12036

P49841

0

phosphorylation

down-regulates

0.302

Gsk3beta was shown to phosphorylate at ser-493 in vitro by phosphopeptide mapping and site-directed mutagenesis, and in vivo in hek293 cells. The role of ser-493 phosphorylation is also a question to be addressed in the future. Because the e-segment appears to be involved in filament formation (27, 42), phosphorylation in that region may also play a regulatory role in filament formation. Secondary structure prediction suggests that phosphorylation of ser-493 in combination with following the pro residue interrupts _-helix of the e-segment

SIGNOR-90668

P22888

P10588

0

transcriptional regulation

down-regulates quantity by repression

0.302

Functional analysis showed that EAR2 and EAR3/COUP-TFI repressed the hLHR promoter activity, whereas TR4 activated hLHR gene transcription.

SIGNOR-266216

Q8N726

Q9HCX3

0

transcriptional regulation

down-regulates quantity by repression

0.302

Finally, we show that ZNF304 also directs transcriptional silencing of INK4-ARF in human embryonic stem cells.

SIGNOR-266098

P98066

P17676

0

transcriptional regulation

up-regulates quantity by expression

0.302

In cotransfection experiments, the C/EBP beta protein trans-activated 10-15-fold the cAspAT gene promoter in HepG2 cells.

SIGNOR-254055

O43248

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.302

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260026

P30307

P68400

0

phosphorylation

down-regulates

0.302

Inhibition of protein kinase ck2 enzyme activity in vivo resulted in an enhanced nuclear localization of cdc25c. Thus, phosphorylation of cdc25c at threonine 236 is an important signal for the retention of cdc25c in the cytoplasm

SIGNOR-123713

P52735

Q16620

0

phosphorylation

up-regulates activity

0.302

Finally, the TrkB kinase dependent increase in P-Y172 Vav2 was largely independent of the Vav2 SH2 domain (XREF_FIG, right), which was previously shown to be important for activation by Eph receptors.|These findings reveal a strong kinase independent binding mechanism between Vav and TrkB in cells, and suggest that activation of TrkB kinase activity stimulates Vav2 tyrosine phosphorylation and GEF activity.

SIGNOR-280050

Q8N8S7

Q13976

0

phosphorylation

down-regulates activity

0.302

Vertebrate Ena/VASP proteins are phosphorylated by PKA, as well as PKG, and the phosphorylation is required for full function in a number of cellular contexts. PKG may preferentially phosphorylate sites of Ena/VASP proteins that reduce or inactivate these proteins. Inactivated Ena/VASP proteins dissociate from actin filaments, allowing capping proteins to bind and block monomer addition to plus ends, resulting in filament retraction.

SIGNOR-268288

P19838

P50591

0

post transcriptional regulation

up-regulates quantity by expression

0.302

Treatment with TRAIL increased the NF-κB transcriptional activity by approximately twofold in MDA-MB-231 cells compared to the control.

SIGNOR-277936

Q2M1Z3

P49841

0

phosphorylation

up-regulates activity

0.302

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

SIGNOR-262879