IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels float64 0 2 | mechanism stringclasses 40 values | effect stringclasses 10 values | score float64 0.1 0.99 ⌀ | sentence stringlengths 10 1.63k ⌀ | signor_id stringlengths 12 14 |
|---|---|---|---|---|---|---|---|
P15056 | P27361 | 0 | phosphorylation | down-regulates | 0.645 | Erk-induced phosphorylation of b-raf on t753 promoted the disassembly of raf heterodimers, and the mutation of t753 prolonged growth factor-induced heterodimerization. The b-raf t753a mutant enhanced differentiation of pc12 cells, which was previously shown to be dependent on sustained erk signaling. Site is critical for v-src dependent modulation of slk kinase activity. | SIGNOR-144827 |
Q5H8A4 | Q07326 | 0 | binding | up-regulates quantity by stabilization | 0.645 | We show that the human homolog of Gpi7p, termed hGPI7, binds to and is stabilized by PIG-F and that hGPI7 competes with PIG-O for binding to PIG-F. PIG-F Binds to and Stabilizes hGPI7 and PIG-O Independently. These results are consistent with the hypothesis that overexpression of hGPI7 decreases the biosynthetic activity of PIG-O by decreasing the available PIG-F, thereby destabilizing PIG-O. | SIGNOR-261358 |
P16333 | P22681 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.644 | Taken together, these results show that lysine 178 in Nck1 is the acceptor site for ubiquitin transferred by c-Cbl, and that the ubiquitination of Nck1 by c-Cbl is blocked in the presence of synaptopodin. | SIGNOR-278606 |
P46531 | Q9NR61 | 0 | binding | up-regulates activity | 0.644 | Expression analysis of known notch ligands suggests that dll4 is the only ligand that exhibits spatial and temporal expression consistent with the activation of notch1 and notch4 during vascular development. The identification of dll4 reveals a candidate ligand for notch receptors involved in blood vessel biology | SIGNOR-112649 |
P00748 | P05155 | 0 | binding | down-regulates activity | 0.644 | 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-263517 |
Q9UM47 | P78504 | 0 | binding | up-regulates | 0.644 | Here we report the first x-ray structure of a functional fragment of a notch ligand, the dsl-egf3 domains of human jagged-1 (j-1dsl-egf3). The structure identifies a highly conserved face of the dsl domain and we show, by functional analysis of drosophila ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with notch. | SIGNOR-179625 |
P46531 | Q96J02 | 0 | ubiquitination | down-regulates | 0.644 | Itch binds to the n-terminal portion of the notch intracellular domain via its ww domains and promotes ubiquitination of notch through its hect ubiquitin ligase domain. | SIGNOR-80702 |
Q01082 | Q12955 | 0 | binding | up-regulates activity | 0.644 | Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton. | SIGNOR-266711 |
Q53ET0 | P57059 | 0 | phosphorylation | down-regulates | 0.644 | These results suggested that sik1 could phosphorylate all torcs and thereby repress their transactivation activities. | SIGNOR-147707 |
P08047 | P28482 | 0 | phosphorylation | up-regulates | 0.644 | Here we show that p42/p44 mapk directly phosphorylates sp1 on threonines 453 and 739 both in vitro and in vivo. Mutation of these sites to alanines decreases by half the mapk-dependent transcriptional activity of sp1. Phosphorylated extracellular signal-regulated protein kinases 1 and 2 phosphorylate sp1 on serine 59 and regulate cellular senescence via transcription of p21sdi1/cip1/waf1. | SIGNOR-116158 |
P35222 | Q9HCK8 | 0 | binding | down-regulates | 0.644 | Duplin (axis duplication inhibitor) interacts with beta-catenin and prevents its binding to tcf, thereby inhibiting downstream wnt signaling | SIGNOR-128976 |
O15198 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.644 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degra-dation of smads and receptors for tgf-beta and bmps | SIGNOR-193390 |
O95644 | P11309 | 0 | phosphorylation | up-regulates activity | 0.643 | Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. | SIGNOR-276775 |
Q14653 | Q13526 | 0 | binding | down-regulates quantity by destabilization | 0.643 | Here we report that activation of IRF3 is negatively regulated by the peptidyl-prolyl isomerase Pin1. After stimulation by double-stranded RNA, induced phosphorylation of the Ser339–Pro340 motif of IRF3 led to its interaction with Pin1 and finally polyubiquitination and then proteasome-dependent degradation of IRF3. Suppression of Pin1 by RNA interference or genetic deletion resulted in enhanced IRF-3-dependent production of interferon-beta, with consequent reduction of virus replication. | SIGNOR-252256 |
P30307 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.643 | We also found that activated ATR phosphorylates CDC25C (Cell Division Cycle 25C) at serine 216, which in turn inactivates the cyclin B1/Cyclin-Dependent Kinase 1(CDK1) complex and induces G2-phase arrest. | SIGNOR-279008 |
P50148 | P30556 | 0 | binding | up-regulates activity | 0.643 | 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-257017 |
O60674 | Q9UQQ2 | 0 | binding | down-regulates activity | 0.643 | we identified Lnk as a physiological negative regulator of JAK2 in stem cells and TPO/Mpl/JAK2/Lnk as a major regulatory pathway in controlling stem cell self-renewal and quiescence. we identify a direct interaction between Lnk and the Mpl/JAK2 complex that regulates various HSC functions. | SIGNOR-260075 |
Q15761 | P10082 | 0 | binding | up-regulates | 0.643 | Maml3 forms complexes in vivo with icn and csl and functiosn as transcriptional coactivators for notch signaling. | SIGNOR-114749 |
P12931 | Q16825 | 0 | dephosphorylation | up-regulates | 0.643 | Ptpd1 activates src tyrosine kinase and increases the magnitude and duration of epidermal growth factor (egf) signaling. | SIGNOR-124774 |
P30304 | Q13535 | 0 | phosphorylation | down-regulates activity | 0.643 | ATR and CHK1 mediated loss of CDC25A activity suspends CDKs, such as CDK2, in an inactive phosphorylated state, blocking initiation of DNA replication origins.|In the presence of replication stalling, activated CHK1 and ATR phosphorylates CDC25A and promotes its degradation. | SIGNOR-280183 |
P46527 | Q00535 | 0 | phosphorylation | down-regulates activity | 0.643 | CDK5 knockdown in HEY cells significantly prolonged the half-life of TP53 and p27 Kip1 proteins (XREF_FIG).|During neural stem cell differentiation, CDK5 can phosphorylate p27 at Thr187 and at Ser10, promoting neurite outgrowth as neurons differentiate . | SIGNOR-279681 |
Q15797 | O00238 | 0 | phosphorylation | up-regulates | 0.643 | 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-187190 |
P51692 | P06239 | 0 | phosphorylation | up-regulates activity | 0.643 | A constitutively active Lck kinase promotes cell proliferation and resistance to apoptosis through signal transducer and activator of transcription 5b activation.|Expression of the active Lck kinase induces both tyrosine phosphorylation and DNA binding activity of signal transducer and activator of transcription 5b (STAT5b), a STAT family member activated in a variety of tumor cells. | SIGNOR-279056 |
P38936 | Q00987 | 0 | binding | down-regulates quantity by destabilization | 0.643 | MDM2 facilitates p21 degradation independent of ubiquitination and the E3 ligase function of MDM2. Instead, MDM2 promotes p21 degradation by facilitating binding of p21 with the proteasomal C8 subunit. The physical interaction between p21 and MDM2 was demonstrated both in vitro and in vivo with the binding region in amino acids 180-298 of the MDM2 protein. | SIGNOR-272954 |
Q01196 | P15976 | 0 | binding | up-regulates activity | 0.643 | We and others have previously shown that RUNX1 and GATA-1 physically interact and cooperate in the activation of megakaryocytic promoters such as alpha IIb integrin and glycoprotein Ibalpha. In particular, we will elaborate on recent data which suggest that GATA-1 targets RUNX1 for modification, in particular phosphorylation by cyclin-dependent kinases. Furthermore, targeting of RUNX1 by GATA-1 for phosphorylation may convert RUNX1 from a repressor to an activator. This is a potential mechanism of transcriptional cooperation and may be an essential step in megakaryocytic differentiation. | SIGNOR-254194 |
P61586 | Q9P107 | 0 | gtpase-activating protein | down-regulates activity | 0.643 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260505 |
P01308 | P52945 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.643 | In conclusion, Pdx1 confers the expression of pancreatic β-cell-specific genes, such as genes encoding insulin, islet amyloid polypeptide, Glut2, and Nkx6.1. | SIGNOR-255541 |
Q16665 | Q00987 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.643 | We find that p53 promotes Mdm2-mediated ubiquitination and proteasomal degradation of the HIF-1alpha subunit of hypoxia-inducible factor 1 (HIF-1), a heterodimeric transcription factor that regulates cellular energy metabolism and angiogenesis in response to oxygen deprivation. | SIGNOR-271385 |
Q9NPB6 | O14641 | 0 | binding | up-regulates | 0.643 | In pcp , dvl binds to proteins such as pkc, atypical pkc (apkc), dvl-associated activator of morphogenesis 1 (daam1), dvl-associating protein with a high frequency of leu residues (daple) and partitioning defective 6 (par6), which are important for the regulation of small gtpases such as rho and rac and, consequently, the cytoskeleton and cell polarity58. | SIGNOR-199500 |
P01588 | Q16665 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.643 | Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix transcription factor that regulates hypoxia-inducible genes including the human erythropoietin (EPO) gene. | SIGNOR-253695 |
P25090 | P04083 | 0 | binding | up-regulates activity | 0.643 | We show that the mimetic N-terminal annexin 1 peptide Ac1-25 is able to activate and desensitize not only FPR but also FPRL1 and FPRL2. | SIGNOR-259437 |
P01019 | P08311 | 0 | cleavage | up-regulates activity | 0.643 | Cathepsin G, elastase, and proteinase 3 are serine proteinases released by activated neutrophils. Cathepsin G can cleave angiotensinogen to release angiotensin II, but this activity has not been previously reported for elastase or proteinase 3. In this study we show that elastase and proteinase 3 can release angiotensin I from angiotensinogen and release angiotensin II from angiotensin I and angiotensinogen. | SIGNOR-256312 |
Q13705 | O14793 | 0 | binding | up-regulates activity | 0.642 | The purified C-terminal myostatin dimer was capable of binding the activin type II receptors, Act RIIB and, to a lesser extent, Act RIIA | SIGNOR-235153 |
Q92574 | O14920 | 0 | phosphorylation | down-regulates | 0.642 | Here we show that ikkbeta, a major downstream kinase in the tnfalpha signaling pathway, physically interacts with and phosphorylates tsc1 at ser487 and ser511, resulting in suppression of tsc1phosphorylation of tsc2 (by akt and erk;refs. 28, 29) and tsc1(by ikkbeta;ref. 30) results in the disruption of the tsc1/2 complex, and thereby activates the oncogenic mtor signaling contributing to tumor progression. | SIGNOR-157296 |
P36896 | Q96S42 | 0 | binding | up-regulates activity | 0.642 | Nodal effects are dependent upon interactions with Cripto, a small cysteine-rich extracellular protein that is attached to the plasma membrane through a glycosyl phosphatidyl inositol linkage. Cripto interacts with Nodal and ALK4, independently, and promotes the formation of a stable high affinity complex with activin type II receptors. | SIGNOR-251939 |
O60343 | P31751 | 0 | phosphorylation | down-regulates activity | 0.642 | AKT2 phosphorylation blocks AS160 function enhancing GLUT4 intracellular vesicular transport, and as such promotes glucose uptake following insulin release .|Notable mechanisms promoting this involves AKT2 mediated phosphorylation of the Rab-GTPase-activating protein TBC1D4, also known as AS160. | SIGNOR-280179 |
P30291 | P53350 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.642 | In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1. | SIGNOR-276040 |
P46527 | Q13616 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.642 | Furthermore, c-myc activation can also promote the degradation of p27kip1 protein by directly activating the cul1 gene, which encodes a critical component of the ubiquitin ligase scfskp2 | SIGNOR-102725 |
P27037 | P13385 | 0 | binding | down-regulates | 0.642 | Here we show that cripto can form a complex with activin and actrii/iib cripto inhibited crosslinking of activin to alk4 and the association of alk4 with actrii/iib. | SIGNOR-100052 |
Q9UPR3 | Q9BY41 | 0 | binding | up-regulates quantity by stabilization | 0.642 | Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation. | SIGNOR-272650 |
Q6ZNA4 | O15169 | 0 | binding | up-regulates | 0.642 | Here, we show that axin activates tgf-beta signaling by forming a multimeric complex consisting of smad7 and ubiquitin e3 ligase arkadia. Axin is a scaffold protein in tgf-beta signaling that promotes degradation of smad7 by arkadia. | SIGNOR-119660 |
P46531 | P78504 | 0 | binding | up-regulates activity | 0.642 | We identify functional fragments of human notch-1 (n-1) and jagged-1 (j-1) which interact in a calcium-dependent manner. | SIGNOR-219253 |
O15027 | Q92734 | 0 | binding | up-regulates | 0.642 | We identify tfg-1, a new conserved regulator of protein secretion that interacts directly with sec-16 and controls the export of cargoes from the endoplasmic reticulum in caenorhabditis elegans. Hydrodynamic studies indicate that tfg-1 forms hexamers that facilitate the co-assembly of sec-16 with copii subunits. | SIGNOR-173242 |
Q8IVT5 | P27448 | 0 | phosphorylation | down-regulates activity | 0.642 | C-TAK1 phosphorylates KSR1 at S392, forming a 14-3-3 binding site.|In mammalian cells, C-TAK1 has been shown to negatively regulate KSR1 by phosphorylation of Ser392. | SIGNOR-279225 |
P35637 | Q92973 | 0 | relocalization | up-regulates activity | 0.642 | The C-terminal nuclear localization sequence of FUsed in Sarcoma (FUS-NLS) is critical for its nuclear import mediated by transportin (Trn1). | SIGNOR-262101 |
Q16659 | Q9UNH5 | 0 | dephosphorylation | down-regulates | 0.641 | Using ms analysis, we identified four novel phosphorylation sites, ser684, ser688, thr698 and ser705, located at the extreme c-terminus of erk3.alanine substitution of the four c-terminal phosphorylation sites markedly decreased the half-life of erk3 in mitosis, thereby linking phosphorylation to the stabilization of the kinase.we found that the phosphatases cdc14a and cdc14b (cdc is cell-division cycle) bind to erk3 and reverse its c-terminal phosphorylation in mitosis. | SIGNOR-164412 |
P16949 | P06493 | 0 | phosphorylation | up-regulates activity | 0.641 | null | SIGNOR-279803 |
O14640 | Q76N89 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.641 | We have also found that NEDL1 targets Dishevelled-1 (Dvl1) for ubiquitination-mediated degradation and that mutant (but not wild-type) SOD1 affects the function of Dvl1. | SIGNOR-271499 |
O14640 | Q9Y283 | 0 | ubiquitination | down-regulates | 0.641 | Inversin inhibits the canonical wnt pathway by targeting cytoplasmic dishevelled (dsh or dvl1) for degradation | SIGNOR-135766 |
P01112 | P50148 | 0 | binding | up-regulates | 0.641 | Galfaq/11 subunits also activate p21ras | SIGNOR-50104 |
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 |
O60266 | P38405 | 0 | binding | up-regulates activity | 0.641 | Subsequently, the Gaolf subunit activates the integral membrane protein adenylyl cyclase type III (AC3), leading to the conversion of adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP) | SIGNOR-278072 |
Q14191 | P78527 | 0 | phosphorylation | up-regulates | 0.641 | Here, we identify ser-440 and -467 in wrn as major phosphorylation sites mediated by dna-pk our findings indicate that phosphorylation of ser-440 and -467 in wrn are important for relocalization of wrn to nucleoli, and that it is required for efficient dsb repair. | SIGNOR-203737 |
Q92997 | Q14332 | 0 | binding | up-regulates activity | 0.641 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258962 |
P56704 | Q5T9L3 | 0 | relocalization | up-regulates activity | 0.641 | WNT secretion requires its binding to the carrier protein wntless (WLS); | SIGNOR-256599 |
Q92997 | Q13467 | 0 | binding | up-regulates activity | 0.641 | Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling. | SIGNOR-258963 |
Q9UJU6 | P43403 | 0 | phosphorylation | up-regulates | 0.64 | We found an interaction between the tyrosine kinase zap-70 and hip-55, which was induced by tcr stimulation. Zap-70 phosphorylated hip-55 at tyr-334 and tyr-344, which were shown to be the tyrosine phosphorylation sites of hip-55 in stimulated t cells.Our results demonstrate for the first time that hip-55 is an important adaptor protein for the jnk kinase cascade in tcr signaling. | SIGNOR-118695 |
Q14332 | O00744 | 0 | binding | up-regulates | 0.64 | Inhibition of adipogenesis by wnt10b is likely mediated by wnt receptors, frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 7 | SIGNOR-89137 |
P09471 | P35372 | 0 | binding | up-regulates activity | 0.64 | 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-256990 |
Q5TCZ1 | P12931 | 0 | phosphorylation | up-regulates activity | 0.64 | First, we observed that the co-expression of both activated Src and wild-type Tks5 stimulated gelatin degradation beyond that of Tks5 overexpression alone ( ).|In melanoma cells Src dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck, for Nck recruitment to invadopodia, and for invadopodia associated matrix degradation activity . | SIGNOR-280134 |
P01106 | Q13485 | 0 | transcriptional regulation | down-regulates quantity by repression | 0.64 | Down-regulation of c-Myc is a critical event for growth inhibition induced by transforming growth factor-β (TGF-β) and is frequently impaired in cancer cells. We determined a Smad-responsive element in the c-mycpromoter. | SIGNOR-251493 |
P61586 | P36897 | 0 | null | up-regulates activity | 0.64 | Thus, TGF-_1 rapidly stimulates activity of both RhoA and Rac1 and this activation requires ALK5/T_RI kinase activity. | SIGNOR-227499 |
Q9GZV9 | Q8IXL6 | 0 | phosphorylation | down-regulates activity | 0.64 | Here we show that Fam20C directly phosphorylates FGF23 on Ser(180) | Our above results support, phosphorylation of FGF23 at Ser180 inhibits O-glycosylation and would therefore promote hormone proteolysis and thus inactivation. | SIGNOR-260925 |
P63000 | P52757 | 0 | gtpase-activating protein | down-regulates activity | 0.64 | We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2). | SIGNOR-260500 |
Q9NPG1 | P56704 | 0 | binding | up-regulates activity | 0.64 | Here we focus on the role of Wnts, their putative receptors Frizzled and the soluble antagonist Frzb1 in regulating mammalian myogenesis. Although it is becoming evident that the signaling downstream of Frizzled receptors is much more complex than anticipated, it is conceivable that it may lead to transcriptional activation of Myf5 and MyoD and to initiation of myogenesis. | SIGNOR-73039 |
Q9UMX1 | Q99835 | 0 | binding | down-regulates activity | 0.64 | In addition to activating g(i), smo signals through its c-terminal tail to inhibit suppressor of fused, resulting in stabilization and activation of the gli family of transcription factors, which execute a transcriptional response to so-called canonical hh signaling. | SIGNOR-177656 |
O43819 | P04637 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.64 | P53 regulates basal expression of AIF and SCO2 and facilitates oxidative phosphorylation. The expression of GLUT1, GLUT4, and HK2 is negatively regulated by p53, whereas TIGAR expression is induced by p53. The net result of p53-mediated regulation of these glycolytic enzymes is the suppression of glycolysis. In addition, p53 directly binds and inhibits G6PD activity and downregulates the pentose phosphate pathway. | SIGNOR-267463 |
P18848 | P05198 | 0 | transcriptional regulation | down-regulates quantity | 0.64 | ER stress, viral infection, and other cellular stress signals activate PERK, PKR, HRI, and GCN2 kinases that converge on phosphorylation of eIF2alpha, the core of ISR. This leads to global attenuation of Cap Âdependent translation while concomitantly initiates the preferential translation of ISR Âspecific mRNAs, such as ATF4. ATF4 is the main effector of the ISR. eIF2alpha phosphorylation causes a reduction in global protein synthesis while allowing the translation of selected genes including activating transcription factor 4 (ATF4), aiding cell survival and recovery | SIGNOR-260169 |
O75581 | O14904 | 0 | binding | up-regulates | 0.64 | Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation. | SIGNOR-132076 |
O60674 | P40189 | 0 | phosphorylation | up-regulates activity | 0.639 | All IL-6-type cytokines recruit gp130to their receptot complexes They either signal via gp130 alone [8] or in combination with LIFR [9] or the recently cloned OSMR [10], which are all able to activate Jaks proteins. Two tyrosine residues at the corresponding positions of Jak2 (tyrosine-1007 and tyrosine-1008) were found to be phosphorylated, and a single mutation of tyrosine-1007 eliminated essentially all tyrosine kinase activity [59]. | SIGNOR-238634 |
P00533 | P28482 | 0 | phosphorylation | down-regulates activity | 0.639 | A growth factor-stimulated protein kinase activity that phosphorylates the epidermal growth factor (EGF) receptor at Thr669 has been described Anion-exchange chromatography demonstrated that this protein kinase activity was accounted for by two enzymes. The first peak of activity eluted from the column corresponded to the microtubule-associated protein 2 (MAP2) kinase | SIGNOR-20545 |
P49815 | Q9NX09 | 0 | binding | up-regulates activity | 0.639 | Redd1 is a negative regulator of mTOR, mediating dissociation of 14-3-3 from tuberous sclerosis complex (TSC)2, which allows formation of a TSC-TSC2 complex. | SIGNOR-277469 |
Q04721 | P78504 | 0 | binding | up-regulates | 0.639 | Here we report the first x-ray structure of a functional fragment of a notch ligand, the dsl-egf3 domains of human jagged-1 (j-1dsl-egf3). The structure identifies a highly conserved face of the dsl domain and we show, by functional analysis of drosophila ligand mutants, that this surface is required for both cis- and trans-regulatory interactions with notch. | SIGNOR-81364 |
Q99961 | P12931 | 0 | phosphorylation | down-regulates | 0.639 | Further, we identified an interaction between fak's second pro-rich motif and endophilin a2's sh3 domain. This interaction served as an autophosphorylation-dependent scaffold to allow src phosphorylation of endophilin a2 at tyr315. Tyr315 phosphorylation inhibited endophilin/dynamin interactions, and blockade of tyr315 phosphorylation promoted endocytosis of mt1-mmp. Together, these results suggest a regulatory mechanism of cell invasion whereby fak promotes cell-surface presentation of mt1-mmp by inhibiting endophilin a2-dependent endocytosis. | SIGNOR-139150 |
O75581 | Q8NCW0 | 0 | binding | down-regulates | 0.639 | Here we show that the transmembrane proteins kremen1 and kremen2 are high-affinity dkk1 receptors that functionally cooperate with dkk1 to block wnt/beta-catenin signalling. Kremen2 forms a ternary complex with dkk1 and lrp6, and induces rapid endocytosis and removal of the wnt receptor lrp6 from the plasma membrane. | SIGNOR-88894 |
P28715 | P54727 | 0 | binding | up-regulates activity | 0.639 | GG-NER is initiated by the GG-NER specific factor XPC-RAD23B, in some cases with the help of UV-DDB (UV-damaged DNA-binding protein). TC-NER is initiated by RNA polymerase stalled at a lesion with the help of TC-NER specific factors CSA, CSB, and XAB2. Both pathways require the core NER factors to complete the excision process|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000).|The core NER dual incision reaction has been reconstituted in vitro with purified factors using XPC-RAD23B, TFIIH, XPA, RPA, XPG, and ERCC1-XPF (Aboussekhra et al. 1995; Mu et al. 1995; Araujo et al. 2000). Functional studies revealed that XPC-RAD23B is the initial damage recognition factor in this system, as the presence of XPC-RAD23B is required for assembly of the other core NER factors and progression through the NER pathway both in vitro and in vivo | SIGNOR-275702 |
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 |
P46734 | Q9Y6R4 | 0 | phosphorylation | up-regulates activity | 0.639 | These results, therefore, suggest that mtk1 directly phosphorylates and activates mkk3, mkk6 and sek1. | SIGNOR-50891 |
Q9UJU2 | Q04725 | 0 | binding | down-regulates | 0.638 | Mapping studies reveal that groucho/tle binds two regions in lef-1. | SIGNOR-185736 |
Q13042 | P06493 | 0 | phosphorylation | up-regulates | 0.638 | Apc activation is thought to depend on apc phosphorylation and cdc20 binding. We have identified 43 phospho_sites on apc of which at least 34 are mitosis specific. Of these, 32 sites are clustered in parts of apc1 and the tetratricopeptide repeat (tpr) subunits cdc27, cdc16, cdc23 and apc7. In vitro, at least 15 of the mitotic phospho_sites can be generated by cyclin_dependent kinase 1 (cdk1), and 3 by polo_like kinase 1 (plk1). Apc phosphorylation by cdk1, but not by plk1, is sufficient for increased cdc20 binding and apc activation | SIGNOR-119762 |
P45983 | Q13387 | 0 | binding | up-regulates | 0.638 | These experiments demonstrated that 10 different jnk isoforms bound to both jip proteins. | SIGNOR-70860 |
Q9H0H5 | P53350 | 0 | phosphorylation | up-regulates | 0.638 | Tandem mass spectrometry analysis of a purified hscyk-4 fragment (hscyk-4n) phosphorylated by plk1 in vitro identified four major sites (s157, s170, s214, and s260 plk1 phosphorylation of hscyk-4 localizes ect2 at the midzone and stimulates rhoa-dependent contractile ring assembly at the equatorial cortex. | SIGNOR-185758 |
Q02556 | P19474 | 0 | ubiquitination | down-regulates quantity | 0.638 | From these results, we concluded that TRIM21 down-regulated IRF8 and enhanced the secretion of IL-12/23p40 in BD monocytes.|IRF8 is ubiquitinated by TRIM21, which promotes secretion of IL-12/23p40 after TLR/IFN-\u03b3 stimulation xref . | SIGNOR-278791 |
Q9Y496 | P32121 | 0 | binding | up-regulates | 0.638 | Betaarrestin 2 was subsequentialy shown to bridge smo to the kinestesin motor kif3 to promote ciliary accumulation of smo in mammalian cells | SIGNOR-199107 |
P52732 | P06493 | 0 | phosphorylation | up-regulates activity | 0.638 | Nek6 phosphorylated Eg5 at several sites in vitro and one of these sites, Ser1033, is phosphorylated in vivo during mitosis. Whereas CDK1 phosphorylates nearly all Eg5 at Thr926 during mitosis, Nek6 phosphorylates approximately 3% of Eg5, primarily at the spindle poles. | SIGNOR-273887 |
P16333 | P09619 | 0 | binding | up-regulates | 0.638 | Growth factor binding to receptor protein tyrosine kinases (r-ptks)1 induces their dimerization and trans-phosphorylation, creating docking sites for proteins containing sh2 and ptb protein interaction domains. Nck binds to the pdgf and egfr receptors (figure 3c). | SIGNOR-64737 |
P01137 | Q14766 | 0 | binding | up-regulates activity | 0.638 | Together these data form strong support for the hypothesis that the LTBP plays an essential role in the activation of latent TGF-b in heterotypic cultures. | SIGNOR-235754 |
P67775 | O43815 | 0 | binding | up-regulates activity | 0.638 | The striatin family proteins interact with the structural (A) and catalytic (C) subunits of the protein phosphatase, PP2A, and are also termed the B‴ family of PP2A subunits (4). Within heterotrimeric PP2A complexes, striatins function as one of many regulatory B subunits thought to be responsible for substrate selection and localization of PP2A isoforms | SIGNOR-261698 |
P23458 | P16871 | 0 | binding | up-regulates | 0.638 | For instance, jak1 is associated with the ? Subunits of ?c Cytokines such as il-7r? And IL-4R. jak3 is associated with the ?c20,21. Cytokine binding mediates the trans-phosphorylation of receptor associated jak kinases, which in turn phosphorylate tyrosine residues on the receptors themselves. The receptor phosphotyrosines serve as docking sites for sh2 domain proteins including the stat family of transcription factors which are activated by jak-mediated phosphorylation. | SIGNOR-178494 |
O15524 | P42226 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.638 | We found that IL-4, like IFN-gamma, induces rapid de novo expression of SOCS-1 in primary macrophages. Induction of SOCS-1 gene expression by IL-4 is STAT6-dependent. | SIGNOR-249570 |
P01189 | P40763 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.638 | We show that phospho-STAT3 activates POMC promoter in response to leptin signaling through a mechanism that requires an SP1-binding site in the POMC promoter. | SIGNOR-263497 |
Q9UJV9 | P19474 | 0 | ubiquitination | down-regulates quantity | 0.638 | Furthermore, overexpression of TRIM21 in mDCs led to lower expression of DDX41 in these mDCs and up to 70% less IFN-beta production by mDCs in response to intracellular DNA (XREF_FIG).|Here we report that the E3 ligase TRIM21 negatively regulated the type I interferon response in myeloid dendritic cells (mDCs) and monocytes that had been induced by cytosolic double stranded DNA (dsDNA), mainly by promoting the ubiquitination and degradation of DDX41. | SIGNOR-278790 |
Q9HAT8 | Q9NWZ3 | 0 | phosphorylation | up-regulates | 0.638 | Pellino2 is one of the firstsubstrates identified for irak1 andirak4. | SIGNOR-103717 |
P04150 | P45983 | 0 | phosphorylation | down-regulates | 0.638 | Taken together, these findings suggest that jnk-mediated phosphorylation of the gr-ser226 enhances gr nuclear export and may contribute to termination of gr-mediated transcription. | SIGNOR-93558 |
P29317 | P22681 | 0 | binding | down-regulates quantity by destabilization | 0.638 | In our present study, we demonstrate that ligand-mediated stimulation causes EphA2 to be internalized and degraded. The mechanism of this response involves ligand-mediated autophosphorylation of EphA2, which promotes an association between EphA2 and the c-Cbl adaptor protein. We also show that c-Cbl promotes stimulation-dependent EphA2 degradation. | SIGNOR-272590 |
Q15796 | Q9UPN9 | 0 | binding | up-regulates activity | 0.638 | The ubiquitious nuclear protein transcriptional intermediary factor 1gamma (tif1gamma) selectively binds receptor-phosphorylated smad2/3 in competition with smad4. Rapid and robust binding of tif1gamma to smad2/3 occurs in hematopoietic, mesenchymal, and epithelial cell types in response to tgfbeta. Tif1gamma mediates the differentiation response while smad4 mediates the antiproliferative response with smad2/3 participating in both responses. | SIGNOR-236064 |
Q9H0E2 | Q9NPH3 | 0 | binding | down-regulates activity | 0.638 | Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1β treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip–IRAK complexes to the activated receptor complex occurs through association of Tollip with IL-1RAcP. Co-recruited MyD88 then triggers IRAK autophosphorylation, which in turn leads to rapid dissociation of IRAK from Tollip (and IL-1Rs) | SIGNOR-251979 |
Q13415 | P06493 | 0 | phosphorylation | up-regulates | 0.637 | Horc1p contains three (s/t)px(k/r) consensus sites for cdk phosphorylation (ser258, ser273, and thr375). These data combined strongly suggest that skp2 promotes horc1p turnover and that the n-terminal domain of horc1p, containing most of the phosphorylation sites and overlapping with one of the skp2-interacting domains, is a regulatory element for horc1p stability. | SIGNOR-116329 |
P04049 | P27361 | 0 | phosphorylation | down-regulates activity | 0.637 | Here, we identify six residues of Raf-1 (S29, S43, S289, S296, S301, and S642) that become hyperphosphorylated in a manner coincident with Raf-1 inactivation. | Five of the identified sites are proline-directed targets of activated ERK, and phosphorylation of all six sites requires MEK signaling, indicating a negative feedback mechanism. Hyperphosphorylation of these six sites inhibits the Ras/Raf-1 interaction and desensitizes Raf-1 to additional stimuli.|FLAG-Raf-1 phosphorylated by activated ERK2 | SIGNOR-143688 |
P08581 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.637 | It has been reported that the protein tyrosine phosphatase PTP1B could inactivate MET by direct dephosphorylation of Tyr 1234 and 1235 in its activation loop, and that this dephosphorylation takes place in peri-nuclear region of the cell [ xref ]. | SIGNOR-277001 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.