IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
Q12772 | P28482 | 0 | phosphorylation | up-regulates | 0.358 | Insulin-activated erk-mitogen-activated protein kinases phosphorylate sterol regulatory element-binding protein-2 at serine residues 432 and 455 in vivo.Further characterization by electrophoretic mobility shift assay and promoter reporter gene analyses revealed that phosphorylation does not influence protein/dna interaction, but enhances trans-activity. | SIGNOR-123045 |
Q00987 | O75417 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | DNA polymerase eta is targeted by Mdm2 for polyubiquitination and proteasomal degradation in response to ultraviolet irradiation | SIGNOR-272729 |
Q15796 | O95405 | 0 | relocalization | up-regulates activity | 0.908 | Smad anchor for receptor activation (SARA) is known as Smad cofactor that interacts directly with Smad2/3 and functions to recruit Smad2/3 to the TGF-beta receptor. | SIGNOR-165786 |
Q99759 | Q13501 | 1 | phosphorylation | up-regulates activity | 0.556 | MEKK3 overexpression, but not that of a kinase dead mutant, was able to induce the phosphorylation of p62 at T269 and S272 (XREF_FIG), which correlated with mTORC1 activation (XREF_FIG), suggesting that MEKK3 could be a bona fide regulator of p62 phosphorylation and mTORC1 activity. | SIGNOR-279532 |
P78368 | O15534 | 1 | phosphorylation | down-regulates | 0.394 | Ck1_ and ck1_2 can promote proteasome-dependent per1 degradation in mammalian tissue culture cells, and their removal by rnai leads to an increased abundance of per1. | SIGNOR-137751 |
Q99466 | Q969H0 | 0 | ubiquitination | down-regulates | 0.499 | We show here that the f-box/wd40 repeat protein sel-10 negatively regulates notch receptor activity by targeting the intracellular domain of notch receptors for ubiquitin-mediated protein degradation. in conclusion, hsel-10 physically associates with mouse notch4(int-3) through the wd40 domain, whereas the f-box domain is not required for this interaction. | SIGNOR-110955 |
P19838 | P04150 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.6 | We have described how the receptor uses several means to achieve repression of the genes regulated by AP-1 and NF-KB proteins | SIGNOR-251680 |
Q15835 | Q8IVF5 | 1 | phosphorylation | down-regulates activity | 0.2 | For example, RhoK phosphorylates and inhibits TIAM1, STEF, and PAR3; disrupts the polarity complex; and prevents Rac activation ( xref ). | SIGNOR-279997 |
P80370 | Q01094 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Using luciferase reporter assay, ChIP assay and EMSA, we found that the -211/-194 region of the pref-1 promoter is essential for the binding of E2F1 as well as E2F1-dependent transcriptional activation. | SIGNOR-271684 |
P29474 | Q04759 | 0 | phosphorylation | down-regulates activity | 0.2 | The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites | SIGNOR-251636 |
Q9Y4K3 | Q92985 | 1 | ubiquitination | up-regulates activity | 0.732 | We have shown that TRAF6 E3 ligase promotes IRF7 K63-linked ubiquitination that is required for EBV LMP1 activation of IRF7 [ xref ]; however, A20, a member with both E3 ligase and deubiquitinase activities in the OTU family, inhibits LMP1-stimulated IRF7 activity by acting as a deubiquitinase [ xref ]. | SIGNOR-278788 |
P00533 | Q92952 | 1 | phosphorylation | up-regulates activity | 0.2 | These results demonstrate the novel information that hSKCa1 channels are inhibited by genistein, T25 and AG556 via EGFR tyrosine kinase inhibition, which is related to the phosphorylation of Tyr(109) in the N-terminus. | SIGNOR-276490 |
P06493 | Q9ULW0 | 1 | phosphorylation | down-regulates activity | 0.637 | In this study, we characterize the phosphorylation of threonine 72 (Thr(72)) in human TPX2, a residue highly conserved across species. We find that Cdk1/2 phosphorylate TPX2 in vitro and in vivo. |Endogenous TPX2 phosphorylated at Thr(72) does not associate with the mitotic spindle. Furthermore, ectopic GFP-TPX2 T72A preferentially concentrates on the spindle | SIGNOR-265096 |
P52630 | P23470 | 0 | dephosphorylation | up-regulates activity | 0.2 | PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity. | SIGNOR-254728 |
Q13555 | O43318 | 1 | phosphorylation | up-regulates | 0.2 | Camkii interacts with and phosphorylates tak1. | SIGNOR-96422 |
P10636 | P30153 | 0 | dephosphorylation | down-regulates | 0.2 | Galpha12 directly interacts with pp2a: evidence for galpha12-stimulated pp2a phosphatase activity and dephosphorylation of microtubule-associated protein, tau. | SIGNOR-130136 |
Q9NTG7 | P04179 | 1 | deacetylation | up-regulates activity | 0.654 | SOD2 is the key substrate of SIRT3 in mitochondria. The combination of SIRT3 and SOD2 leads to the deacetylation and activation of SOD2 | SIGNOR-267646 |
P04637 | P45984 | 0 | phosphorylation | up-regulates | 0.747 | These findings strongly suggest that jnks are the major direct signaling mediators of uvb-induced p53 phosphorylation at serine 20. furthermore, phosphorylation of p53 at serine 20 by uvb-activated jnks and uvb-induced p53-dependent transcriptional activity were suppressed in jnk1 or jnk2 knockout (jnk1(-/-) or jnk2(-/-)) cells. | SIGNOR-115835 |
P31947 | O95863 | 1 | relocalization | down-regulates | 0.2 | Pkd1 phosphorylates ser(11) (s11) on transcription factor snail, a master emt regulator and repressor of e-cadherin expression, triggering nuclear export of snail via 14-3-3_ binding | SIGNOR-168540 |
P31749 | P13631 | 1 | phosphorylation | up-regulates activity | 0.467 | S379 of RARγ is indispensable for the CLDN6-triggered cellular events. The most important finding of the present study is that the CLDN6/SFK/PI3K/AKT signaling controls the RARγ and ERα activities (Fig. 6). | SIGNOR-277492 |
P06493 | Q93008 | 1 | phosphorylation | up-regulates activity | 0.279 | Here, we find that CDC14B antagonizes CDK1-mediated activating mitotic phosphorylation of the deubiquitinase USP9X at serine residue 2563, which we show to be essential for USP9X to mediate mitotic survival. Starting from an unbiased proteome-wide screening approach, we specify Wilms' tumor protein 1 (WT1) as the relevant substrate that becomes deubiquitylated and stabilized by serine 2563-phosphorylated USP9X in mitosis. | SIGNOR-275608 |
Q96GD4 | Q8WWK9 | 1 | phosphorylation | up-regulates | 0.296 | Here, we report that tmap is a novel substrate of the aurora b kinase. Ser627 of tmap was specifically phosphorylated by aurora b both in vitro and in vivo. Nearly all mutations at the phosphorylation motif had dramatic effects on the subcellular localization of tmap. | SIGNOR-165410 |
P50458 | P01215 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.266 | In Cos cells, LH-2 activated the a-subunit promoter approximately twofold | SIGNOR-266055 |
P49023 | P45983 | 0 | phosphorylation | up-regulates activity | 0.676 | JNK1 phosphorylates serine 178 on paxillin, a focal adhesion adaptor, both in vitro and in intact cells. NBT-II cells expressing the Ser 178 --> Ala mutant of paxillin (Pax(S178A)) formed focal adhesions and exhibited the limited movement associated with such contacts in both single-cell-migration and wound-healing assays. In contrast, cells expressing wild-type paxillin moved rapidly and retained close contacts as the predominant adhesion. | SIGNOR-250129 |
Q16539 | Q99626 | 1 | phosphorylation | down-regulates quantity by destabilization | 0.414 | ERK2, p38alpha and GSK-3beta can phosphorylate Cdx2 in vitro and that the 4S motif is required for phosphorylation by GSK-3beta and p38alpha|Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its ubiquitin-dependent proteasome degradation | SIGNOR-250092 |
Q99626 | Q02817 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | COS-7 cells were transiently transfected with a CDX1 or CDX2 expression construct and then used for the luciferase assay, reverse transcription-polymerase chain reaction, and electrophoretic mobility shift assay (EMSA). The CDX2 expression construct activated the MUC2 promoter and increased the endogenous MUC2 mRNA level, while the CDX1 one did not. | SIGNOR-253966 |
Q7L9L4 | P54829 | 0 | dephosphorylation | up-regulates activity | 0.2 | PTPN5 dephosphorylates\nMob1a at Y26 residue. | SIGNOR-277058 |
Q02156 | P35236 | 1 | phosphorylation | up-regulates activity | 0.2 | HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. (Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient. | SIGNOR-276050 |
Q9NS56 | P53350 | 0 | phosphorylation | up-regulates activity | 0.445 | Plk1-mediated phosphorylation of topors regulates p53 stabilityherein, we have identified topoisomerase i-binding protein (topors), a p53-binding protein, as a plk1 target. We show that plk1 phosphorylates topors on ser(718) in vivo. Significantly, expression of a plk1-unphosphorylatable topors mutant (s718a) leads to a dramatic accumulation of p53 through inhibition of p53 degradation. Topors is an ubiquitin and small ubiquitin-like modifier ubiquitin-protein isopeptide ligase (sumo e3) ligase. Plk1-mediated phosphorylation of topors inhibits topors-mediated sumoylation of p53, whereas p53 ubiquitination is enhanced, leading to p53 degradation. | SIGNOR-185838 |
Q12968 | Q9Y625 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. | SIGNOR-264024 |
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 |
P37275 | P09467 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Down-regulation of FBP1 by ZEB1-mediated repression confers to growth and invasion in lung cancer cells|we confirmed DNA methylation in the promoter contributed to the decrease of FBP1 expression in lung cancer cells. We identified Zinc finger E-box-binding homeobox 1 (ZEB1) bond to FBP1 promoter to enhance DNA methylation in lung cancer cells. | SIGNOR-267596 |
P49760 | Q07955 | 1 | phosphorylation | up-regulates activity | 0.298 | In vitro, Clk/Sty efficiently phosphorylated the SR family member ASF/SF2 on serine residues located within its serine/arginine-rich region (the RS domain). Overexpression of the active Clk/Sty kinase caused a redistribution of SR proteins within the nucleus. These results suggest that Clk/Sty kinase directly regulates the activity and compartmentalization of SR splicing factors. | SIGNOR-273858 |
P08631 | P19174 | 1 | phosphorylation | up-regulates activity | 0.681 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-249361 |
Q13627 | P98177 | 1 | phosphorylation | down-regulates | 0.315 | Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity | SIGNOR-183677 |
P25098 | Q13188 | 1 | phosphorylation | up-regulates activity | 0.2 | Taken together, these studies support a role for GRK2 phosphorylation of Mst2 residues Ser-18 and Ser-316 in EGF-promoted centrosome separation.|Thus GRK2 appears to mediate EGF promoted cleavage and activation of Mst2. | SIGNOR-278206 |
P49841 | P19838 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.388 | GSK-3 beta forms an in vivo complex with and specifically phosphorylates NF-kappa B1/p105 at Ser-903 and Ser-907 in vitro. GSK-3 beta has a dual effect on p105: it stabilizes p105 under resting conditions and primes p105 for degradation upon tumor necrosis factor (TNF)-alpha treatment. Indeed, constitutive processing of p105 to p50 occurs at a higher rate in cells lacking GSK-3 beta with respect to wild-type cells and can be reduced upon reintroduction of GSK-3 beta by transfection. S903A and S907A point mutations impair p105 proteolysis in response to TNF-α. | SIGNOR-251251 |
Q02750 | P27361 | 1 | phosphorylation | up-regulates | 0.752 | Mek1 as indicated by extensive phosphorylation of erk1 and erk2 during the initial 2 h of adipogenesis. | SIGNOR-210176 |
P56945 | P51813 | 0 | phosphorylation | up-regulates quantity | 0.506 | Recombinant Bmx kinase was found to effectively phosphorylate the wt CAS SH3 domain on Tyr-12 (Figure 2B). A novel phosphorylation site on CAS, Tyr-12 (Y12) within the ligand-binding hydrophobic pocket of the CAS SH3 domain, was identified and found to be enriched in Src-transformed cells and invasive human carcinoma cells. | SIGNOR-276384 |
P84022 | Q9GZU7 | 0 | dephosphorylation | up-regulates activity | 0.433 | SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity | SIGNOR-248792 |
P19484 | P42345 | 0 | phosphorylation | down-regulates activity | 0.477 | Our data points to the lysosome as the site where mTORC1-dependent phosphorylation of TFEB occurs. [...]Our study has revealed a specific role for phosphorylation of TFEB S211 in the negative regulation of the nuclear abundance of TFEB. This occurs through the promotion of 14-3-3 binding and the masking of the nearby NLS on TFEB. | SIGNOR-248270 |
Q96EP1 | P51532 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.333 | 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-271457 |
Q99612 | P49841 | 0 | phosphorylation | up-regulates activity | 0.2 | Functionally, GSK3beta enhanced KLF6 mediated growth suppression, which was abrogated by the KLF6-4A phosphomutant.|These data establish that GSK3\u03b2 directly phosphorylates KLF6, which augments its induction of p21 and resultant growth suppression. | SIGNOR-279373 |
P17252 | Q86UR1 | 1 | phosphorylation | down-regulates | 0.29 | Phosphorylation of nadph oxidase activator 1 (noxa1) on serine 282 by map kinases and on serine 172 by protein kinase c and protein kinase a prevents nox1 hyperactivation. | SIGNOR-163667 |
Q7Z419 | P38936 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.359 | P53RFP, a p53-inducible RING-finger protein, regulates the stability of p21WAF1. Here we report the isolation of a novel transcriptional target of p53, designated p53RFP (p53-inducible RING-finger protein), whose product has E3 ubiquitin ligase activity. Its expression was negatively correlated to that of p21(WAF1) protein; p53RFP is likely to play a role in the regulation of this protein, probably through interaction with, and ubiquitination of, p21(WAF1). | SIGNOR-271478 |
P54259 | P53779 | 0 | phosphorylation | down-regulates activity | 0.2 | Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-jun nh2-terminal kinase. serine 734 of the drpla protein is a phospho-acceptor site by jnk. The phosphorylation may be coupled to the activation of a protease. The molecular size of drpla protein detected in the rat brain with the specific phosphopeptide antibody was 150_kda, which was slightly smaller than that expected from the sequence and the results with the human protein. The phosphorylated forms of ha-tagged human drpla gradually disappeared after osmotic treatment, | SIGNOR-102394 |
Q12852 | O14950 | 1 | phosphorylation | up-regulates | 0.2 | Zip kinase (hzipk) phosphorylated the regulatory light chain of myosin ii (mrlc) at both ser19 and thr18 in vitro. In this study, we demonstrate that hzipk also induces the diphosphorylation of mrlc in nonmuscle cells. | SIGNOR-113664 |
Q14493 | P06493 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.419 | Phosphorylation of threonine 61 by cyclin a/Cdk1 triggers degradation of stem-loop binding protein at the end of S phase | SIGNOR-265258 |
P11831 | P49137 | 0 | phosphorylation | up-regulates | 0.584 | Neverthless, some transcription factors, such as e47, er81, srf and creb are also phosphorylated by mk2 | SIGNOR-166640 |
Q8NEA6 | Q96J02 | 0 | ubiquitination | down-regulates quantity | 0.331 | Itch promotes proteolytic degradation of Glis3.|Since Itch interacts with and ubiquitinates Glis3, it was of interest to determine which regions were necessary for Itch directed degradation of Glis3. | SIGNOR-278653 |
Q9P2A4 | O00308 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | The AIP2 E3 ligase acts as a novel negative regulator of ABA signaling by promoting ABI3 degradation. Here, we show that ABI3 is an unstable protein and that an ABI3-interacting protein (AIP2), which contains a RING motif, can polyubiquitinate ABI3 in vitro. | SIGNOR-272656 |
O15550 | P09017 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.467 | 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-260030 |
Q13118 | P29597 | 0 | phosphorylation | down-regulates activity | 0.438 | These data strongly supported that Tyk2 phosphorylates TIEG1.|Tyrosine kinase Tyk2-mediated phosphorylation of TIEG1 at Tyr179 promoted noncanonical K-27-linked polyubiquitination, which inhibited TIEG1 nuclear translocation. | SIGNOR-279575 |
P41091 | P49770 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.696 | EIF2B converts the protein synthesis initiation factor 2 (eIF2) from an inactive GDP-bound form to an active eIF2-GTP complex owing to its guanine nucleotide exchange factor (GEF) activity. | SIGNOR-269135 |
P12830 | P56524 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.287 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275663 |
Q5T0T0 | P79483 | 1 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Two E3 ligases, MARCH I and MARCH VIII, have been shown to polyubiquitinate lysine residue 225 in the cytoplasmic tail of I-Abeta and HLA-DRbeta. We show that lysine residue 219 in the cytoplasmic tail of DRalpha is also subject to polyubiquitination. | SIGNOR-271408 |
Q05397 | P08069 | 1 | phosphorylation | up-regulates quantity | 0.535 | Taken together, our data suggest that FAK mediates the phosphorylation of IGF-1R and stabilizes the receptor.In this study we demonstrate that FAK, mainly known for its role in integrin signaling pathways, associates with and phosphorylates IGF-1R independently of IGF-1R 's intrinsic tyrosine kinase activity.|The impact of FAK on the expression levels of IGF-1R could be multilateral | SIGNOR-279565 |
P12931 | Q05209 | 0 | dephosphorylation | up-regulates activity | 0.542 | PTP-PEST increases dephosphorylation of Src at Y527 and activates it.|The data presented here supports our hypothesis that PTP-PEST activates Src via dephosphorylating it at Y527 (Tyr530 in human c-Src equivalent to Tyr527 in chicken Src). | SIGNOR-277086 |
Q9Y6K1 | P19544 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.379 | Here, we show that Wilms' tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms' tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression. | SIGNOR-255904 |
Q99683 | Q06124 | 0 | dephosphorylation | up-regulates | 0.367 | Previously we have shown that tyrosine 718 of ask1 when phosphorylated is critical for socs1 binding and socs1-mediated degradation of ask1we identified jak2 and shp2 as a tyr-718-specific kinase and phosphatase, respectively. | SIGNOR-184604 |
P60484 | Q86TM6 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | Secondly, HRD1 promotes PTEN ubiquitination and degradation. | SIGNOR-278724 |
Q8TDN4 | P31749 | 0 | phosphorylation | down-regulates activity | 0.34 | Here, we report that Cables1 levels are controlled by a phosphorylation and 14-3-3-dependent mechanism. Mutagenic analyses identified two residues, T44 and T150, that are specifically critical for 14-3-3 binding and that serve as substrates for phosphorylation by the cell survival kinase Akt, which by binding directly to Cables1 recruits 14-3-3 to the complex.Ectopic expression of activated Akt (AKT1) prevented Cables1-induced apoptosis. | SIGNOR-276756 |
P08235 | P27361 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.35 | Taken together, these data suggest that ERK1/2 directly phosphorylates the MR on several serine residues present in its NTD, that the upward shift of MR is mainly due to receptor phosphorylation, and finally that these sites represent the major aldosterone-inducible targets for MR phosphorylation.MR phosphorylation limits the transcriptional activity.Taken together, these results provide evidence that MR phosphorylation plays a role in aldosterone-mediated ubiquitylation and degradation. | SIGNOR-276102 |
Q00987 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.522 | We found that a major kinase responsible for s407 phosphorylation is atrs407 phosphorylation of mdm2 by atr reduces mdm2-dependent export of p53 from nuclei to cytoplasm. | SIGNOR-119546 |
P26038 | P61586 | 0 | phosphorylation | up-regulates activity | 0.61 | Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies. | SIGNOR-268431 |
O15264 | P05787 | 1 | phosphorylation | up-regulates | 0.2 | Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif . Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase. The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis. | SIGNOR-114075 |
P30622 | Q38SD2 | 0 | phosphorylation | up-regulates activity | 0.398 | LRRK1 phosphorylates CLIP-170 at Thr1384, located in its C-terminal zinc knuckle motif, and this promotes the association of CLIP-170 with dynein-dynactin complexes. | SIGNOR-275469 |
P16104 | Q99502 | 0 | dephosphorylation | down-regulates | 0.2 | Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3. | SIGNOR-168879 |
Q9HC98 | P35613 | 1 | phosphorylation | down-regulates activity | 0.2 | These results indicate that NEK6 directly interacts with CD147 and phosphorylates the protein at serine-252 in Huh-7 cells. | SIGNOR-273882 |
O76064 | O95999 | 1 | ubiquitination | up-regulates quantity by stabilization | 0.328 | Phosphorylated and ubiquitinated BCL10 is stabilized on the damage sites through binding to and presenting UBC13 to RNF168.|We thus concluded that BCL10 is ubiquitinated mainly with K63-linked ubiquitination by RNF8. | SIGNOR-278778 |
Q13049 | Q01860 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.268 | This further supports that TRIM32 and Oct4 do physically interact, so that TRIM32 can specifically ubiquitinate Oct4 and thereby target it for degradation. | SIGNOR-278620 |
P68400 | P12259 | 1 | phosphorylation | down-regulates activity | 0.307 | Factor Va, the essential cofactor for prothrombinase, is phosphorylated on the acidic COOH terminus of the heavy chain of the cofactor, at Ser692, by a platelet membrane-associated casein kinase II (CKII). | The phosphorylated cofactor has increased susceptibility to inactivation by activated protein C, since phosphorylated factor Va was found to be inactivated approximately 3-fold faster than its native counterpart. | SIGNOR-250862 |
P53667 | Q16566 | 0 | phosphorylation | up-regulates activity | 0.256 | An active form of CaMKIV but not CaMKI enhanced Thr 508 phosphorylation of LIMK1 and increased the kinase activity of LIMK1.|Taken together, our results suggest that LIMK1 mediated cofilin phosphorylation is critical for ionomycin induced neurite outgrowth and that CaMKIV mediates ionomycin induced LIMK1 activation. | SIGNOR-280201 |
P28329 | P05129 | 0 | phosphorylation | up-regulates | 0.321 | We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation. | SIGNOR-129320 |
P53350 | Q9Y6D9 | 1 | phosphorylation | up-regulates activity | 0.464 | These findings indicate mechanistic roles contributed by protein phosphorylation and Plk1 to the SAC activity of Mad1.Here, we have studied the phosphorylation of Mad1 and mapped using liquid chromatography-tandem mass spectrometry several phosphorylated amino acids in this protein. One phosphorylated residue, Thr680, was characterized to be important for the kinetochore localization of Mad1 and its SAC function. | SIGNOR-276173 |
P53350 | Q16143 | 1 | phosphorylation | down-regulates activity | 0.318 | Polo-like kinase (plk) family (plk1, plk2, and plk3) phosphorylate alpha-syn and beta-syn specifically at ser-129 and ser-118, respectively. Polo-like kinase 2 (plk2) phosphorylates alpha-synuclein at serine 129 in central nervous system. The membrane association of pd-linked mutant alpha -synuclein, but not wild-type -synuclein, was increased by serine 129 phosphorylation. | SIGNOR-176079 |
P15923 | Q9H2X6 | 0 | phosphorylation | down-regulates activity | 0.2 | This result provides a mechanistic explanation for the context-dependent function of HIPK2 in Wnt signaling | SIGNOR-279193 |
O00238 | O15198 | 1 | phosphorylation | up-regulates activity | 0.708 | Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression. | SIGNOR-255264 |
P35968 | P29353 | 1 | relocalization | up-regulates activity | 0.711 | In a similar fashion, KDR associates with Grb2 and Nck in a ligand-dependent fashion, suggesting Shc, Grb2, and Nck as potential candidates involved in the regulation of endothelial function. | SIGNOR-261949 |
P28562 | P05412 | 1 | dephosphorylation | down-regulates activity | 0.455 | However, adenovirus mediated overexpression of MKP-1 only slightly decreased JNK and c-Jun phosphorylation compared with the severe inactivation of JNK activities induced by MKK7 knockdown.|The results suggested that HDACI-induced MKP-1 contributes to inactivation of JNK instead of ERK, consistent with the previous reports in other cell types | SIGNOR-277102 |
P54646 | P12931 | 0 | phosphorylation | down-regulates activity | 0.258 | We show here that Src signaling leads to direct phosphorylation of the AMPK-α subunit on a novel site, tyrosine 179, resulting in suppression of AMPK-T172 phosphorylation and autophagy upon integrin-mediated cell adhesion. | SIGNOR-277573 |
P46934 | P37231 | 1 | ubiquitination | up-regulates activity | 0.386 | First, NEDD4 interacts with and ubiquitinates PPARgamma.|NEDD4 increases PPARgamma stability through the inhibition of its proteasomal degradation. | SIGNOR-278540 |
P28329 | Q02156 | 0 | phosphorylation | up-regulates | 0.312 | We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation | SIGNOR-129312 |
Q04206 | Q9Y2K7 | 0 | demethylation | down-regulates | 0.459 | Fbxl11 and nsd1 have opposite effects on nf-kb; both bind to p65 subunit after activation of nf-kb. / nsd1 activates nf-kb and reverses the inhibitory effect of fbxl11 / these data confirm that fbxl11 and nsd1 constitute an enzyme pair that methylates and demethylates p65 on k218 and 221 in response to cytokine stimulation. | SIGNOR-163384 |
P67870 | O60763 | 1 | phosphorylation | up-regulates activity | 0.335 | Phosphorylation is mediated by casein kinase II (CKII) or a CKII-like kinase. | Serine 941 in the Acidic Domain of p115 Is Essential for Reassembly of Golgi Cisternae | SIGNOR-251082 |
Q14289 | P06396 | 1 | phosphorylation | down-regulates activity | 0.527 | Our results demonstrate that PYK2 inhibits this EGTA stable gelsolin-actin monomer association.|PYK2 phosphorylates gelsolin at tyrosine residues and regulates gelsolin bioactivity, including decreasing gelsolin binding to actin monomer and increasing gelsolin binding to phosphatidylinositol lipids. | SIGNOR-278325 |
P25490 | P12931 | 0 | phosphorylation | down-regulates activity | 0.284 | YY1 phosphorylation is mediated by Src family kinases. | SIGNOR-276940 |
P42345 | P30622 | 1 | phosphorylation | up-regulates activity | 0.567 | By contrast to the phosphorylation of p150 Glued by PKA, inhibition of mTOR by rapamycin inhibited the ability of CLIP-170 to bind to microtubules, suggesting that phosphorylation by mTOR promotes CLIP-170 microtubule binding.|The new study confirms this physical interaction in animal cells and suggests that mTOR phosphorylates CLIP-170 on some, but not all, of the sites that are phosphorylated in vivo. | SIGNOR-279231 |
P21730 | P05771 | 0 | phosphorylation | down-regulates | 0.2 | Dynamics of protein kinase c-mediated phosphorylation of the complement c5a receptor on serine 334. Analysis of c5ar ser/ala mutants that possess a single intact serine residue either at position 334 or at neighboring positions 327, 332, or 338 revealed functional redundancy of c-terminal phosphorylation sites since all 4 serine residues could individually support c5ar internalization and desensitization | SIGNOR-151011 |
P46527 | P49841 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.389 | GSK-3\u03b2 phosphorylates p27 Kip1 at S160 and S161, resulting in increased p27 Kip1 stability [ xref ]. | SIGNOR-278938 |
Q9BZL6 | P24723 | 0 | phosphorylation | up-regulates | 0.2 | Thus, pkd2 is likely to be a novel downstream target of specific pkcs upon the stimulation of ags-b cells with gastrin. Our data suggest a two-step mechanism of activation of pkd2 via endogenously produced diacylglycerol and the activation of pkcs. | SIGNOR-89431 |
P06396 | P42574 | 0 | cleavage | down-regulates | 0.639 | Caspase-3 mediates cleavage of gelsolin, generating a fragment that severs actin filaments in an unregulated fashion. The cleavage of gelsolin causes cells to round up, detach and undergo nuclear fragmentation. | SIGNOR-51652 |
P78415 | P17302 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.278 | Irx3 directly represses Cx43 transcription | SIGNOR-266044 |
P29803 | Q15120 | 0 | phosphorylation | down-regulates | 0.563 | Pdh2 was found to be very similar to pdh1 / in the mechanism of inactivation by phosphorylation of three sites;and (iv) in the phosphorylation of sites 1 and 2 by pdk3 / (ser-264 (site 1), ser-271 (site 2), and ser-203 (site 3) | SIGNOR-143974 |
Q8IYK4 | P08123 | 1 | glycosylation | up-regulates activity | 0.4 | Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues. | SIGNOR-261157 |
P68400 | Q13224 | 1 | phosphorylation | down-regulates | 0.324 | Here we show that casein kinase ii (ck2) phosphorylates the serine residue (ser1480) within the c-terminal pdz ligand (iesdv) of the nr2b subunit of nmdar in vitro and in vivo. Phosphorylation of ser1480 disrupts the interaction of nr2b with the pdz domains of psd-95 and sap102 and decreases surface nr2b expression in neurons. | SIGNOR-130336 |
P53350 | Q15208 | 1 | phosphorylation | down-regulates activity | 0.316 | Here, we identified a conserved signaling axis in which NDR1 kinase activity is regulated by PLK1 in mitosis. PLK1 phosphorylates NDR1 at three putative threonine residues (T7, T183 and T407) at mitotic entry, which elicits PLK1-dependent suppression of NDR1 activity and ensures correct spindle orientation in mitosis. | SIGNOR-276914 |
P04049 | P36507 | 1 | phosphorylation | up-regulates | 0.733 | To understand the mechanism of activation of MAPKK, we have identified Ser217 and Ser221 of MAPKK1 as the sites phosphorylated by p74raf-1. | SIGNOR-36553 |
P05771 | O15530 | 0 | phosphorylation | up-regulates | 0.522 | One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated. | SIGNOR-126069 |
P58012 | Q96EB6 | 0 | deacetylation | down-regulates | 0.501 | We find that foxl2 activity is repressed by the sirt1 deacetylase. | SIGNOR-182306 |
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