IdA string | IdB string | labels int64 | mechanism string | effect string | score float64 | sentence string | signor_id string |
|---|---|---|---|---|---|---|---|
P09467 | O75385 | 0 | phosphorylation | down-regulates activity | 0.2 | Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown). | SIGNOR-274031 |
Q9NRM7 | O14965 | 0 | phosphorylation | up-regulates | 0.38 | On the basis of these observations, we conclude that s83 of lats2 is a phosphorylation target of aurora-a and this phosphorylation plays a role of the centrosomal localization of lats2. | SIGNOR-124830 |
P10451 | P15036 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.251 | We demonstrated that Ets2 is capable of binding to and transactivating the OPN promoter using gel shift and transient transfection assays | SIGNOR-259872 |
P12318 | P43405 | 0 | phosphorylation | up-regulates activity | 0.673 | To identify the FcgammaRII-phosphorylating protein tyrosine kinase (PTK), we used the combination of an in vitro and an in vivo approach. In an in vitro assay using recombinant cytoplasmic tails of the different FcgammaRII isoforms as well as tyrosine exchange mutants, we show that each of the BCR-associated PTKs (Lyn, Blk, Fyn, and Syk) shows different phosphorylation patterns with regard to the different FcgammaR isoforms and pointFyn and Blk definitely phosphorylate Y-282 in the ITAM of Fc_RIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addi-tion to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-298) because altering this tyrosine residue together with one of the tyrosine residues clearly shown to be phosphorylated by the respective PTK results in the abrogation of phosphorylation. | SIGNOR-247590 |
P31947 | P46937 | 1 | relocalization | down-regulates activity | 0.461 | Verteporfin increases the level of 14-3-3σ, which promotes the translocation of YAP from nucleus to cytoplasm. | SIGNOR-278130 |
P24941 | P33991 | 1 | phosphorylation | down-regulates activity | 0.767 | We reported that the dna helicase activity of the human and mouse mcm4-6-7 complex, a sub-complex of the mcm2-7 heterohexamer, is inhibited by the phosphorylation by cdk2-cyclin a we identified six sites, including ser-32, ser-53, and thr-109, in the amino-terminal region of mouse mcm4 that are required for the phosphorylation with cdk2-cyclin a. | SIGNOR-100881 |
O75581 | O94921 | 0 | phosphorylation | up-regulates | 0.333 | Low-density lipoprotein receptor related proteins 5 and 6 (lrp5/6) are transmembrane receptors that initiate wnt/beta-catenin signaling. Phosphorylation of pppsp motifs in the lrp6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide rnai screen, we show that pppsp phosphorylation requires the drosophila cyclin-dependent kinase (cdk) l63. L63 and its vertebrate homolog pftk are regulated by the membrane tethered g2/m cyclin, cyclin y, which mediates binding to and phosphorylation of lrp6. | SIGNOR-162924 |
Q9NQB0 | P19784 | 0 | phosphorylation | up-regulates activity | 0.378 | We show here that Tcf-4 can be phosphorylated in vitro by protein kinase CK2 stoichiometrically in amino acids Ser-58-Ser-59-Ser-60. Phosphorylation of these residues does not modify the interaction of Tcf-4 with beta-catenin but reduces its association to plakoglobin. | Experiments performed using a Tcf-4 mutant with decreased interaction to plakoglobin demonstrated that binding to this protein negatively affected the transcriptional activity of Tcf-4. | SIGNOR-251044 |
P51812 | Q9Y4K3 | 1 | phosphorylation | up-regulates activity | 0.272 | These results demonstrate that TRAF6 K63 ubiquitination might be regulated by an RSK2 mediated phosphorylation dependent mechanism and phosphorylation of TRAF6 at Ser46, 47 and 48 enhances its ubiquitin mediated inflammation signaling. | SIGNOR-278302 |
P01106 | P49841 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.72 | Phosphorylation of Thr 58, likely mediated by GSK-3 but dependent on the prior phosphorylation of Ser 62, is associated with degradation of Myc. | SIGNOR-252080 |
P60484 | P16220 | 1 | dephosphorylation | down-regulates activity | 0.436 | Our study demonstrates that PTEN can dephosphorylate CREB at Ser133 and that PTEN protein phosphatase activity is required for CREB dephosphoryation.|Moreover, we use both in vitro and in vivo experiments to show PTEN can dephosphorylate CREB in a phosphatase-dependent manner, suggesting that CREB is a substrate of PTEN nuclear phosphatase. Loss of Pten results in an elevated RNA level of multiple CREB transcriptional targets and increased cell proliferation, which can be reversed by a nonphosphorylatable CREB mutant or knockdown of CREB. These data reveal a mechanism for PTEN modulation of CREB-mediated gene transcription and cell growth. | SIGNOR-248543 |
P09619 | Q07912 | 1 | phosphorylation | up-regulates activity | 0.359 | Mutational analysis suggested that Y635 of ACK1 is a PDGFR-β phosphorylation site and that the ACK1 Y635F mutant abrogated the sequential activation of AKT. | SIGNOR-276854 |
Q9NY65 | Q8NG68 | 0 | tyrosination | down-regulates | 0.31 | Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization | SIGNOR-176930 |
Q16644 | Q14457 | 1 | phosphorylation | up-regulates activity | 0.425 | Taken together, these data indicate that MK2 and MK3 directly phosphorylate Beclin 1 S90 in vitro, and that MK2 like kinase activity also mediates starvation induced Beclin 1 S90 phosphorylation in cultured cells. | SIGNOR-279342 |
P49459 | P12004 | 1 | ubiquitination | up-regulates | 0.476 | Pcna is mono-ubiquitinated through rad6 and rad18, modified by lysine-63-linked multi-ubiquitination--which additionally requires mms2, ubc13 and rad5--and is conjugated to sumo by ubc9. The first of these is monoubiquitination of lysine 164 on one or more of the pcna subunits by the e2-e3 complex of rad6-rad18. | SIGNOR-92737 |
O75444 | P49840 | 0 | phosphorylation | up-regulates | 0.2 | We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity. | SIGNOR-159358 |
P13631 | P31749 | 0 | 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 |
P25054 | O60729 | 0 | dephosphorylation | up-regulates | 0.2 | The phosphatase cdc14b translocates from the nucleolus to the nucleoplasm and induces the activation of the ubiquitin ligase apc/ccdh1 | SIGNOR-179636 |
Q12778 | O00330 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.2 | Our genetic analysis indicates that Foxo1 is an effector of Irs2 signaling in pancreatic β cells. Foxo1 inactivation leads to increased Pdx1 expression and β cell proliferation. Since Foxo1 is expressed in a subset of cells embedded within pancreatic ducts, we propose that, in quiescent duct-associated cells that are not committed to a β cell fate, Foxo1 acts as a transcriptional brake on Pdx1. We propose the following mechanism of Foxo1 regulation: small quantities of insulin are released in the pancreatic duct (31), where they activate signaling (32) in the Foxo1-positive duct cell subset, leading to Foxo1 nuclear exclusion and Pdx1 expression. | SIGNOR-278151 |
Q9HBI1 | Q13418 | 0 | phosphorylation | up-regulates activity | 0.965 | These results indicate that affixin directly associates with \u03b1-actinin only when its CH2 domain is phosphorylated by ILK.|This may indicate that phosphorylation of the CH2 domain by ILK induces a conformational change of the CH2 domain of affixin, which enables affixin to interact with alpha-actinin to evoke the subsequent maturation of the FA complex. | SIGNOR-278259 |
P0DPK2 | Q92830 | 0 | acetylation | down-regulates activity | 0.2 | The HAT module within the SAGA and ADA complexes acetylates histone H3, mainly on residues K9 and K14. | SIGNOR-269597 |
Q13153 | P19086 | 1 | phosphorylation | up-regulates | 0.2 | Phosphorylation of either ser(16) by pak1 or ser(27) by pkc decreased the affinity of galpha(z) for gbetagamma;phosphorylation of both residues by pkc caused no further effect. Pak1 thus regulates galpha(z) function by attenuating the inhibitory effects of both gaps and gbetagamma. | SIGNOR-48673 |
Q13555 | Q9UQL6 | 1 | phosphorylation | down-regulates | 0.428 | Camk phosphorylates serines -259 and -498 in hdac5, which subsequently serve as docking sites for 14-3-3. Our studies suggest that 14-3-3 binding to hdac5 is required for camk-dependent disruption of mef2hdac complexes and nuclear export of hdac5, and implicate 14-3-3 as a signal-dependent regulator of muscle cell differentiation. | SIGNOR-85102 |
P31749 | Q15173 | 0 | dephosphorylation | down-regulates | 0.661 | Activation of pp2a is the intermediate step between the abeta-ceramide cascade and the subsequent inactivation of akt. | SIGNOR-252615 |
P28482 | Q969V6 | 1 | phosphorylation | down-regulates | 0.2 | Serum induces rhoa-dependent translocation of mkl1 from the cytoplasm to the nucleus and also causes a rapid increase in mkl1 phosphorylation. Serum-induced phosphorylation of the serum response factor coactivator mkl1 by the extracellular signal-regulated kinase 1/2 pathway inhibits its nuclear localization. | SIGNOR-195153 |
Q12923 | P00519 | 1 | dephosphorylation | down-regulates activity | 0.39 | We also found that PTPN13 dephosphorylates and inhibits c-Abl.|While the above results indicated that calpain-2 could cleave PTPN13 and that PTPN13 could dephosphorylate c-Abl at tyrosine 245, they did not determine whether calpain-2-mediated cleavage of PTPN13 resulted in its inactivation and increased tyrosine phosphorylation of c-Abl at tyrosine 245. | SIGNOR-277012 |
Q96BF3 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | We observed that IGPR-1 is activated by shear stress and tensile force and that flow shear stress-mediated IGPR-1 activation modulates remodeling of endothelial cells. Mechanistically, shear stress stimulated activation of AKT Ser/Thr kinase 1 (AKT1), leading to phosphorylation of IGPR-1 at Ser-220. | SIGNOR-273481 |
Q16236 | P04179 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.45 | BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2 | SIGNOR-254652 |
P06213 | O14654 | 1 | phosphorylation | up-regulates activity | 0.518 | The binding of insulin to the subunit of IR not only concentrates insulin at its site of action, but also induces conformational changes in the receptor, which in turn stimulates the tyrosine kinase activity intrinsic to the _ subunit of the IR and triggers the signaling cascades (Fig. 3). Insulin receptors trans phosphorylate several immediate substrates (on Tyr residues) including IRS1-4, Shc, and Gab 1, Cbl, APS, and P60dok. | SIGNOR-217897 |
Q12986 | P01903 | 1 | transcriptional regulation | down-regulates quantity by repression | 0.396 | A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor | SIGNOR-266224 |
P11309 | Q9UNQ0 | 1 | phosphorylation | up-regulates activity | 0.36 | Pim-1 kinase phosphorylates BCRP/ABCG2 and thereby promotes its multimerization and drug-resistant activity in human prostate cancer cells|This is further corroborated by our finding that the plasma membrane localization and drug-resistant activity of BCRP were compromised by T362A mutation. | SIGNOR-264420 |
O60381 | P11309 | 0 | phosphorylation | up-regulates activity | 0.2 | Pim-1 binds to and phosphorylates the transcription factor high mobility group box transcription factor 1 (HBP1), activating it. | SIGNOR-277346 |
P35568 | P24394 | 0 | phosphorylation | up-regulates | 0.566 | Irs-1 and a homologous protein, irs-2 (also known as 4-phosphotyrosine substrate), are recruited to phosphorylated y497 of IL-4R After ligand binding, leading to phosphorylation and activation of irs-1 and irs-2. | SIGNOR-100768 |
P35236 | Q05513 | 0 | phosphorylation | up-regulates activity | 0.26 | 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-276047 |
Q6N021 | P22607 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.25 | FGFR3∆7-9, but not wild-type FGFR3, directly interacts with TET2 and phosphorylates TET2 at Y1902 site, leading to the ubiquitination and proteasome-mediated degradation of TET2. | SIGNOR-277535 |
Q13315 | Q8WVD3 | 1 | phosphorylation | up-regulates activity | 0.2 | We further confirm that RNF138 is phosphorylated by ATM at Ser124. | SIGNOR-279505 |
Q92793 | Q16566 | 0 | phosphorylation | up-regulates activity | 0.635 | Ser301 of CBP was identified as a major target of CaMKIV phosphorylation in vitro and in vivo. CaM kinase inhibitors attenuated phosphorylation at Ser301 and blocked CBP-dependent transcription. Additionally, mutation of Ser301 impaired NMDA- and CaMKIV-stimulated transcription. These findings demonstrate that activity-induced CaMKIV signaling contributes to CREB/CBP-dependent transcription by phosphorylating CBP at Ser301. | SIGNOR-250710 |
P25205 | P24941 | 0 | phosphorylation | up-regulates | 0.796 | In this study, we demonstrate that mcm3 is a substrate of cyclin e/cdk2 and can be phosphorylated by cyclin e/cdk2 at thr-722. | SIGNOR-176656 |
Q15011 | P11021 | 1 | relocalization | up-regulates quantity by stabilization | 0.411 | A key inhibitor of the turnover and Nt-arginylation of BiP was HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation. | SIGNOR-261346 |
O15294 | Q9NZJ5 | 0 | phosphorylation | up-regulates activity | 0.2 | Collectively, these results indicate that upon cold and \u03b2-adrenergic stimulation PERK-activated OGT catalyzes the O-GlcNAcylation of CK2\u03b1 and TOM70 which enhances MIC19 import into the mitochondria increasing cristae formation and cell respiration (Figure 7I).|Here, we report that the ER-resident kinase PERK is activated upon cold or \u03b2-adrenergic stimulation and directly phosphorylates OGT. | SIGNOR-279736 |
Q96QF0 | P31749 | 0 | phosphorylation | up-regulates activity | 0.2 | Rabin8 is phosphorylated and activated by Akt in cells grown on stiff ECM. | SIGNOR-277802 |
Q13153 | Q13363 | 1 | phosphorylation | down-regulates activity | 0.403 | Pak1 phosphorylates ctbp selectively on ser158 within a putative regulatory loop, triggering ctbp cellular redistribution and blocking ctbp ak1 superphosphorylates ctbp and inhibits ctbp dehydrogenase activitycorepressor functions. | SIGNOR-103943 |
Q13188 | P53350 | 0 | phosphorylation | down-regulates activity | 0.331 | We conclude that TRIM69A promotes multi-site phosphorylation of MST2.We demonstrate that TRIM69 stimulates formation of an MST2-PLK1 complex and promotes phosphorylation of MST2 at S15, a known PLK1 site. PLK1-mediated MST2 phosphorylation at S15 is necessary for subsequent phosphorylation of NEK2A to dissociate c-NAP1 from daughter centrioles (7). Thus, we provide a new molecular mechanism by which TRIM69 promotes MST2- and PLK1-mediated centrosome disjunction. | SIGNOR-277904 |
Q9UKX2 | P14859 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238757 |
P19525 | Q15172 | 1 | phosphorylation | up-regulates | 0.328 | Phosphorylation of serine 28 by pkr promotes mitochondrial localization of b56alpha, because wild-type but not mutant s28a b56alpha promoted mitochondrial pp2a activity. | SIGNOR-181793 |
Q15835 | P08100 | 1 | phosphorylation | up-regulates activity | 0.923 | That light-dependent phosphorylation of Rho is mediated primarily by RK. Addition of an inhibitory antibody against rhodopsin kinase (RK) lowered phosphorylation at Ser334, Ser338, and Ser343, without changing the ratio between phosphorylation sites. upon illumination, Ser334c, Ser338, and Ser343 are phosphorylated. | SIGNOR-251190 |
O00506 | P46937 | 1 | phosphorylation | up-regulates activity | 0.265 | Collectively, our data demonstrate that loss of STK25 promotes YAP/TAZ activation.|Lastly, we assessed if STK25 is able to promote YAP phosphorylation in the absence of LATS-HM phosphorylation, based on our in vitro kinase assay results. | SIGNOR-278993 |
P04637 | Q9NQ88 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. TIGAR is the only known phosphatase glycolytic modulator regulated by TP53. The current study delineates the role of TIGAR in OXPHOS and glycolytic metabolic reprogramming in breast cancer. | SIGNOR-267365 |
Q15633 | P23443 | 0 | phosphorylation | up-regulates activity | 0.322 | We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. | SIGNOR-274068 |
P62805 | Q4FZB7 | 0 | methylation | down-regulates activity | 0.2 | SUV420H1 and SUV420H2 are two highly homologous enzymes that methylate lysine 20 of histone H4 (H4K20), a mark that has been implicated in transcriptional regulation. | SIGNOR-266651 |
P38936 | P45983 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.672 | The stress-activated protein kinases p38 alpha and jnk1 stabilize p21(cip1) by phosphorylation.|p38 alpha and JNK1 phosphorylated p21 in vivo, and both p38 alpha and JNK1 phosphorylated p21 at Ser(130) in vitro. | SIGNOR-89440 |
P29317 | P24666 | 0 | dephosphorylation | down-regulates activity | 0.66 | The SAM domain tyrosine Y960 which has been implicated in downstream PI3K signaling is dephosphorylated exclusively by HCPTP-B. The activation loop tyrosine (Y772) which directly controls kinase activity is dephosphorylated about six times faster by HCPTP-A. In contrast, the juxtamembrane tyrosines (Y575, Y588 and Y594) which are implicated in both control of kinase activity and downstream signaling are dephosphorylated by both variants with similar rates | SIGNOR-246023 |
P06493 | O60566 | 1 | phosphorylation | up-regulates | 0.777 | Here, we demonstrate that bubr1 is phosphorylated on the cdk1 site t620, which triggers the recruitment of plk1 and phosphorylation of bubr1 by plk1 both in vitro and in vivo. Phosphorylation does not appear to be required for spindle checkpoint function but instead is important for the stability of kinetochore-microtubule (kt-mt) interactions | SIGNOR-157642 |
Q15366 | P28482 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.318 | We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B). | SIGNOR-262912 |
Q13547 | P25490 | 1 | deacetylation | down-regulates activity | 0.798 | Previous studies have established that YY1 interacts with histone acetyltransferases p300 and CREB-binding protein (CBP) and histone deacetylase 1 (HDAC1), HDAC2, and HDAC3. Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs. YY1 was acetylated in two regions: both p300 and PCAF acetylated the central glycine-lysine-rich domain of residues 170 to 200, and PCAF also acetylated YY1 at the C-terminal DNA-binding zinc finger domain. Acetylation of the central region was required for the full transcriptional repressor activity of YY1 and targeted YY1 for active deacetylation by HDACs. | SIGNOR-268835 |
Q9Y253 | Q13535 | 0 | phosphorylation | up-regulates | 0.415 | Atr-mediated phosphorylation of dna polymerase _ is needed for efficient recovery from uv damage. We show that, after uv irradiation, pol_ becomes phosphorylated at ser601 by the ataxia-telangiectasia mutated and rad3-related (atr) kinase. Atr-dependent phosphorylation of pol_ is necessary to restore normal survival and postreplication repair | SIGNOR-171290 |
P31751 | Q9Y2T7 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.2 | In this context, YBX2 is a dual substrate for both AMPK and Akt2. The phosphorylation at Thr115 by AMPK or at Ser137 by Akt2 facilitates YBX2 accumulation in brown adipocytes by decreasing ubiquitination-mediated degradation. | SIGNOR-277869 |
Q92934 | P17252 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of BAD at ser112 and ser136 in the setting of lapatinib treatment was fully restored by PRKACA expression in BT474, SKBr3, and ZR-75-30 cells (XREF_FIG).|We found that neither PRKACA nor PIM1 restored MAPK or PI3K activation after lapatinib or trastuzumab treatment, but rather inactivated the pro apoptotic protein BAD, thereby permitting survival signaling through BCL-XL. | SIGNOR-280080 |
Q99879 | Q14493 | 0 | translation regulation | up-regulates quantity by expression | 0.2 | Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control. | SIGNOR-265390 |
P07814 | P18848 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress. | SIGNOR-269419 |
O15146 | Q9UPQ7 | 0 | ubiquitination | down-regulates quantity | 0.543 | We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Together, these data demonstrate that PDZRN3 is a catalytically active RING-type E3 ubiquitin ligase | SIGNOR-271664 |
Q13315 | Q12888 | 1 | phosphorylation | up-regulates | 0.873 | Here we report phosphorylation of 53bp1 at several novel residues, using mass spectrometry and phospho-specific antibodies, and show that ionising radiation-stimulated phosphorylation of these residues requires atm. | SIGNOR-197615 |
P43405 | O14986 | 1 | phosphorylation | down-regulates activity | 0.2 | We identified spleen tyrosine kinase (Syk), which is activated by oxidants, as a candidate PIP5Kbeta kinase in this pathway, and mapped the oxidant-sensitive tyrosine phosphorylation site to residue 105. The PIP5KbetaY105E phosphomimetic is catalytically inactive and cytosolic, whereas the Y105F non-phosphorylatable mutant has higher intrinsic lipid kinase activity and is much more membrane associated than wild type PIP5Kbeta. | SIGNOR-276227 |
O95863 | Q8NEZ5 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | FBXO22 elicits its antimetastatic effects by targeting SNAIL, a master regulator of EMT and breast cancer metastasis, for ubiquitin-mediated proteasomal degradation in a glycogen synthase kinase 3β phosphorylation-dependent manner. | SIGNOR-273446 |
O96001 | Q13976 | 0 | phosphorylation | up-regulates | 0.656 | Recombinant human G-substrate was phosphorylated efficiently by cGMP-dependent protein kinase exclusively at Thr residues, and it was recognized by antibodies specific for rabbit phospho-G-substrate. The amino acid sequences surrounding the sites of phosphorylation in G-substrate are related to those around Thr-34 and Thr-35 of the dopamine- and cAMP-regulated phosphoprotein DARPP-32 and inhibitor-1, respectively, two potent inhibitors of protein phosphatase 1. | SIGNOR-263148 |
P49759 | P00519 | 1 | phosphorylation | down-regulates | 0.259 | Here, we identify clk1, clk4, mst1, mst2 and ttk (also known as mps1) as novel thr735 kinases in vitro / phosphorylation of thr735 in c-abl is critical for binding to 14-3-3 | SIGNOR-181031 |
O60890 | P63000 | 1 | gtpase-activating protein | up-regulates activity | 0.591 | OPHN-1 colocalized with the actin cytoskeleton in neuronal and glial cells. We have previously shown that OPHN1 stimulates GTPases activity of RhoA, Cdc42, and Rac1 in vitro | SIGNOR-268399 |
P49841 | Q9UM73 | 0 | phosphorylation | up-regulates activity | 0.248 | It has been reported that Alk phosphorylates and activates Gsk3beta in mouse neural crest explants and neuroblastoma cell lines.|Therefore, we tested whether Alk indeed phosphorylates Y279-GSK3\u03b2 in stomach epithelial cells. | SIGNOR-280180 |
Q04760 | P00519 | 0 | phosphorylation | up-regulates activity | 0.2 | We show that Glo1 activity is promoted by phosphorylation on Tyrosine 136 via multiple kinases. Glo1 Y136 is phosphorylated by multiple different kinases including all members of the Src family. Depletion of multiple different kinases led to a partial reduction in Glo1(Y136) phosphorylation. These included members of the Src family (Src, Yes1, FGR, and the related Abl1), and of the FAK, EPHA, FGFR, and VEGFR families (Figure 2B), suggesting phosphorylation of Glo1 on Y136 by multiple different kinases. In vitro kinase assays revealed that all the members of the Src family, as well as Epha5 and VEGFR3, can efficiently phosphorylate recombinant Glo1 on Y136 (Figure 2C–D). | SIGNOR-276187 |
Q12772 | O75874 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.277 | IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells | SIGNOR-253133 |
P43403 | P12931 | 0 | phosphorylation | up-regulates activity | 0.479 | In the cluster, Zap70 will be rapidly phosphorylated by active Src and slowly phosphorylated by autoinhibited, inactive Src.|We provide evidence that clusters harbor a positive feedback loop among Zap70, LAT, and Src-family kinases that binds phosphorylated LAT and further activates Zap70. | SIGNOR-279126 |
Q92945 | Q13315 | 0 | phosphorylation | up-regulates | 0.423 | The atm kinase directly binds to and phosphorylates ksrp, leading to enhanced interaction between ksrp and pri-mirnas and increased ksrp activity in mirna processing | SIGNOR-172127 |
P63000 | P53602 | 0 | lipidation | up-regulates activity | 0.2 | Akt modulated the pathway by phosphorylating mevalonate diphosphate decarboxylase (MDD) at Ser96. These data suggest that Akt regulates Rac1 activity by directly phosphorylating MDD at Ser96, which augments Rac1 geranylgeranylation. | SIGNOR-265892 |
P46734 | Q16539 | 1 | phosphorylation | up-regulates activity | 0.728 | Two human MAP kinase kinases (MKK3 and MKK4) were cloned that phosphorylate and activate p38 MAP kinase. | SIGNOR-232156 |
P43403 | P29350 | 0 | dephosphorylation | down-regulates | 0.588 | We propose that shp1 can dephosphorylate sites in zap-70 and syk that are involved in coupling these kinases to downstream signaling cascades, including erk2 and elements of the il-2 gene. | SIGNOR-70237 |
P34972 | Q8NB16 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Under hyperglycemic conditions, high glucose induced CB2R internalization in a β-arrestin 2-dependent manner; thereafter, MLKL (mixed lineage kinase domain-like), but not receptor-interacting protein kinase 1 or 3, phosphorylated CB2R at serine 352 and promoted CB2R degradation by ubiquitin modification. CB2R transcriptionally repressed necroptosis through interaction with BACH2; in turn, MLKL formed a negative feedback to phosphorylate CB2R. | SIGNOR-274121 |
P49841 | P15941 | 1 | phosphorylation | down-regulates activity | 0.456 | GSK3beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline. Phosphorylation of MUC1 by GSK3beta decreases binding of MUC1 to beta-catenin in vitro and in vivo. | SIGNOR-249356 |
P35222 | O95388 | 1 | transcriptional regulation | up-regulates quantity | 0.2 | This study identifies WISP-1 as a beta-catenin-regulated gene that can contribute to tumorigenesis. The promoter of WISP-1 was cloned and shown to be activated by both Wnt-1 and beta-catenin expression. | SIGNOR-256270 |
Q6VY07 | P68400 | 0 | phosphorylation | up-regulates activity | 0.545 | Phosphorylation of Ser278 by CK2 or a Ser278-->Asp mutation increased the interaction between PACS-1 and cargo, whereas a Ser278-->Ala substitution decreased this interaction. Moreover, the Ser278-->Ala mutation yields a dominant-negative PACS-1 molecule that selectively blocks retrieval of PACS-1-regulated cargo molecules to the TGN. | SIGNOR-250925 |
P23458 | P29350 | 0 | dephosphorylation | down-regulates | 0.646 | We find, for the first time, that shp-1 down-regulates the level of tyk2 kinase in h9 cells and of jak1 kinase in htb26 cells, by accelerating their degradation. | SIGNOR-119197 |
Q9NRC8 | Q6NXT2 | 1 | deacetylation | up-regulates activity | 0.2 | Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37. | SIGNOR-275879 |
O95819 | P42336 | 1 | phosphorylation | down-regulates activity | 0.2 | MST1/2 and HGK inhibit catalytic activity of p110α through phosphorylation at T1061 | SIGNOR-277921 |
P18433 | Q9H267 | 1 | dephosphorylation | down-regulates activity | 0.2 | Here, we report that VPS33B, a host protein involved in vesicle trafficking, is dephosphorylated by PtpA leading to a block of phagosome maturation by M. tuberculosis.|These data suggest that M. tuberculosis PtpA inhibits phagosome maturation.To assess the role of VPS33B in phagosome maturation, we attenuated the expression of endogenous VPS33B expression in THP-1 cells using a siRNA based approach. | SIGNOR-277015 |
Q13315 | Q14676 | 1 | phosphorylation | up-regulates | 0.846 | We show that, in response to ionizing radiation, mdc1 is hyperphosphorylated in an atm-dependent manner, and rapidly relocalizes to nuclear foci that also contain the mre11 complex, phosphorylated histone h2ax and 53bp1. | SIGNOR-98798 |
P24941 | Q5MJ70 | 0 | relocalization | up-regulates activity | 0.791 | Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres | SIGNOR-263310 |
P05412 | P28482 | 0 | phosphorylation | up-regulates activity | 0.79 | Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1. | SIGNOR-201943 |
P35580 | P14859 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation | SIGNOR-238772 |
P28482 | Q05469 | 1 | phosphorylation | up-regulates activity | 0.368 | Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL. | SIGNOR-249413 |
O14641 | Q9NQ66 | 1 | null | up-regulates activity | 0.268 | Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin | SIGNOR-258979 |
P78527 | P03372 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.386 | DNA-PK phosphorylates ERalpha at Ser-118.|Phosphorylation resulted in stabilization of ERalpha protein as inhibition of DNA-PK resulted in its proteasomal degradation. | SIGNOR-279561 |
Q13177 | P43405 | 1 | phosphorylation | up-regulates activity | 0.271 | This is supported by in vitro studies showing that Pak2 phosphorylates and activates Syk. | SIGNOR-279083 |
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 |
Q05682 | Q15746 | 0 | phosphorylation | down-regulates | 0.641 | Phosphorylation of caldesmon by myosin light chain kinase increases its binding affinity for phosphorylated myosin filaments. | SIGNOR-166049 |
O60674 | P00533 | 1 | phosphorylation | up-regulates activity | 0.612 | Tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Our results indicate that the role of EGFR in signalling by growth hormone is to be phosphorylated by Jak2, thereby providing docking sites for Grb2 and activating MAP kinases and gene expression, independently of the intrinsic tyrosine kinase activity of EGFR.  | SIGNOR-251347 |
Q99623 | P17252 | 0 | phosphorylation | down-regulates activity | 0.2 | PKC\u03b1 phosphorylates PHB2-S39. | SIGNOR-279256 |
O15344 | P18031 | 1 | ubiquitination | down-regulates quantity | 0.2 | Proteasome inhibitor treatment diminished the decrease of PTP1B (Figure 5F) caused by TRIM18 overexpression.|TRIM18 Interacts With PTP1B and Promotes PTP1B Ubiquitination. | SIGNOR-278703 |
Q6WCQ1 | Q13464 | 0 | phosphorylation | down-regulates | 0.296 | Enhanced rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of myosin phosphatase (mp).. | SIGNOR-157593 |
P23769 | Q03112 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.359 | Evi1 directly binds to the promoter region of GATA-2 and thus enhances the GATA-2 transcription. | SIGNOR-266062 |
Q5SQI0 | P0DPH7 | 1 | acetylation | up-regulates quantity by stabilization | 0.242 | Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules | SIGNOR-272244 |
Q9UD71 | P23443 | 0 | phosphorylation | up-regulates activity | 0.257 | D1R-PKA appears intact and elevated DARPP-32(pT34) in Rheb(S16H) mice is reduced by S6K1 inhibition (Figure 3).|S6K1 directly phosphorylates DARPP-32. | SIGNOR-279654 |
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