IdA stringlengths 6 21 | IdB stringlengths 6 21 | labels int64 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 |
|---|---|---|---|---|---|---|---|
O75385 | P54646 | 2 | phosphorylation | down-regulates | 0.505 | Here we report that ulk1/2 in turn phosphorylates all three subunits of ampk and thereby negatively regulates its activity. Thus, we propose that ulk1 is not only involved in the induction of autophagy, but also in terminating signaling events that trigger autophagy. In our model, phosphorylation of ampk by ulk1 repres... | SIGNOR-173050 |
O95382 | O95382 | 2 | phosphorylation | up-regulates activity | 0.2 | These results suggested that the induction of ASK2 phosphorylation in the presence of ASK1 is the consequence of autophosphorylation of ASK2. ASK1 thus appears to not only support the effective protein expression but also confer the kinase activity to ASK2. | SIGNOR-260774 |
P35555 | P01137 | 2 | binding | up-regulates quantity | 0.489 | We have discovered that fibrillin-1, which forms extracellular microfibrils, can regulate the bioavailability of transforming growth factor (TGF) beta1, a powerful cytokine that modulates cell survival and phenotype. Altered TGFbeta signaling is a major contributor to the pathology of Marfan syndrome (MFS) and related ... | SIGNOR-251888 |
P06241 | P06241 | 2 | phosphorylation | up-regulates activity | 0.2 | Activated Fyn furthermore undergoes autophosphorylation on Tyr30, Tyr39 and Tyr420. Tyr28 This site is also a Fyn autophosphorylation site When Fyn mutants with Tyr28, Tyr30 or Tyr39 replaced with phenylalanine residues were transfected into NIH3T3 cells a decreased activation after PDGF stimulation was seen, suggesti... | SIGNOR-251167 |
Q8TAB3 | P10589 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | We demonstrated that high expression of COUP-TFI induces MEC cell fate and protocadherin 19 expression. We next demonstrated that COUP-TFI is able to directly bind to a conserved Sp1/COUP-TFI binding site in the Pcdh19 promoter region by chromatin immunoprecipitation (ChIP) (Fig. 6, E and F). | SIGNOR-267223 |
O43463 | Q8N163 | 2 | binding | down-regulates activity | 0.346 | Besides SIRT1, CCAR2 inhibits the activity of the histone-modifying enzymes SUV39H1 and HDAC3 [9, 10], thus playing an important role in chromatin structure regulation. | SIGNOR-267664 |
Q9UIF8 | Q71DI3 | 2 | binding | down-regulates activity | 0.2 | The BAZ2B bromodomain has been shown to bind to acetylated H3K14 (H3K14ac), whose presence at promoter regions is generally associated with gene activation. This suggests a potential role for BAZ2B in transcriptional activation. | SIGNOR-266623 |
P11308 | P30291 | 0 | phosphorylation | down-regulates quantity by destabilization | 0.2 | Here, we demonstrate that DNA damage induces proteasomal degradation of wild-type ERG and TMPRSS2-ERG oncoprotein through ERG threonine-187 and tyrosine-190 phosphorylation mediated by GSK3β and WEE1, respectively. | SIGNOR-277529 |
Q15139 | Q9Y3E5 | 1 | phosphorylation | up-regulates | 0.3 | Overexpression of constitutively active pkd or pkd activation by treatment with phorbol 12-myristate 13-acetate results in phosphorylation of two serine residues (ser5 and ser87) in a form of bit1 that is confined to the cytoplasm and concomitantly increases the apoptotic activity of cytoplasmic bit1 | SIGNOR-180085 |
Q99683 | Q99683 | 2 | phosphorylation | up-regulates activity | 0.2 | Reporter gene assays showed that all three identified in vitro autophosphorylation sites (thr813, thr838, thr842) regulate ask1 signalingmutation of thr838 drastically reduced reporter gene activity when compared to unstimulated control levels. Interestingly, mutation of the other two sites also provided a significant ... | SIGNOR-158431 |
P09619 | P01127 | 2 | binding | up-regulates | 0.906 | Pdgf-b activates both pdgfr-alpha and pdgfr-beta | SIGNOR-107400 |
Q13315 | Q15554 | 2 | binding | down-regulates activity | 0.685 | It is not yet clear how the presence of TRF2 at telomeres averts the activation of the ATM kinase.> In this regard, overexpression of TRF2can dampen the activation of the ATM kinase, even at nontelomeric sites of DNA damage (95). Furthermore, TRF2 can interact with the ATM kinase as well as with the Mre11 complex | SIGNOR-263323 |
P03372 | P62877 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.344 | I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERalpha protein. | SIGNOR-271434 |
Q7Z434 | O95786 | 2 | binding | up-regulates activity | 0.937 | Initially, RIG-I and MDA5 sense dsRNA in the cytoplasm, produced as a by-product of RNA virus replication.Once one or both of these sensors are activated, they interact with a mitochondrial membrane protein called MAVS (mitochondrial antiviral) (also called IPS1, Cardif, and VISA). They signal to the mitochondrial memb... | SIGNOR-260139 |
P55268 | P31276 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.2 | The specificity of binding of these two proteins to the Lamin B2 origin is confirmed by both band-shift and in vitro footprinting assays. In addition, the ability of HOXC10 and HOXC13 to increase the activity of a promoter containing the 74 bp sequence, as assayed by CAT-assay experiments, demonstrates a direct interac... | SIGNOR-261644 |
Q9H4B6 | Q13043 | 2 | binding | up-regulates quantity by stabilization | 0.886 | Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. | SIGNOR-261958 |
P21462 | P25098 | 0 | phosphorylation | down-regulates activity | 0.2 | Phosphorylation of the FPR carboxyl terminus by GRK2 is the result of a high affinity interaction and proceeds in a hierarchical manner. sequential mechanism of phosphorylation beginning with residues 328 and/or 329, followed by residues 331 and/or 332, and finally residues 334 through 339. Attenuation of receptor-med... | SIGNOR-251452 |
P51955 | P62136 | 0 | dephosphorylation | down-regulates | 0.374 | Nek2 is activated by autophosphorylation, and its dephosphorylation is catalyzed by pp1 | SIGNOR-152949 |
P24530 | P19086 | 2 | binding | up-regulates activity | 0.435 | 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- signali... | SIGNOR-257321 |
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-microtu... | SIGNOR-157642 |
Q16611 | O43464 | 1 | relocalization | up-regulates | 0.295 | Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi | SIGNOR-118908 |
O60674 | Q06124 | 2 | phosphorylation | up-regulates activity | 0.793 | Tyrosine residues 304 and 327 in shp-2 are phosphorylated by jaks, and phosphorylated shp-2 can associate with the downstream adapter protein grb2 | SIGNOR-236266 |
Q13873 | P18075 | 2 | binding | up-regulates | 0.804 | In transfected cos-1 cells, osteogenic protein (op)-1/bmp-7, and less efficiently bmp-4, bound to bmpr-ii. Bmpr-ii bound ligands only weakly alone, but the binding was facilitated by the presence of previously identified type i receptors for bmps. Binding of op-1/bmp-7 to bmpr-ii was also observed in nontransfected cel... | SIGNOR-30512 |
P03372 | P06239 | 0 | phosphorylation | up-regulates | 0.382 | On the basis of these data and other reports describing the structure and activity of y537 mutations, as well as knowledge of the three-dimensional structure of the her ligand binding domain, we propose an alternate model wherein y537f mutation favors an open pocket conformation, affecting the estrogen binding kinetics... | SIGNOR-55853 |
P21709 | P20827 | 2 | binding | up-regulates | 0.83 | The eph family receptors and ligands. | SIGNOR-51932 |
Q53EZ4 | P53350 | 0 | phosphorylation | up-regulates | 0.553 | Upon mitotic entry, centrosome dissociation of cep55 is triggered by erk2/cdk1-dependent phosphorylation at s425 and s428. s425/428 phosphorylation is required for interaction with plk1, enabling phosphorylation of cep55 at s436...enabling it to relocate to the midbody to function in mitotic exit and cytokinesis. | SIGNOR-140898 |
Q07817 | Q16611 | 2 | binding | down-regulates | 0.748 | Bax is held in check by mcl1, bcl-2, and either bcl2l1 or bcl2l2, or by all four. They bind a primed conformer of bak or bax | SIGNOR-152983 |
Q13131 | Q12778 | 1 | phosphorylation | up-regulates | 0.446 | The energy sensor amp-activated protein kinase (ampk) has been shown to directly phosphorylate foxo factors at six regulatory sites that are distinct from the akt. | SIGNOR-157941 |
P28482 | Q9HAV4 | 1 | phosphorylation | down-regulates activity | 0.301 | Here we show that ERK suppresses pre-miRNA export from the nucleus through phosphorylation of exportin-5 (XPO5) at T345/S416/S497. After phosphorylation by ERK, conformation of XPO5 is altered by prolyl isomerase Pin1, resulting in reduction of pre-miRNA loading. | SIGNOR-262984 |
Q9NRM7 | Q9Y2J4 | 2 | phosphorylation | down-regulates activity | 0.728 | The N-terminal regions of Amot proteins contain a conserved HXRXXS consensus site for LATS1/2-mediated phosphorylation.|Amot family members. Knockdown of LATS1 and LATS2 endogenously reduced the phosphorylation of Amots detected by the phospho-specific antibodies. Mutation of the serine to alanine within this HXRXXS si... | SIGNOR-272084 |
P19484 | O15297 | 1 | transcriptional regulation | up-regulates quantity by expression | 0.2 | As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes; | SIGNOR-276557 |
O60353 | Q9ULT6 | 0 | ubiquitination | down-regulates quantity | 0.614 | Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6. | SIGNOR-260114 |
P31749 | Q96BF3 | 1 | 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 |
O00512 | Q9Y3Y4 | 2 | binding | up-regulates | 0.907 | Here we report the identification of two segment polarity genes in drosophila, legless (lgs), and pygopus (pygo), and we show that their products are required for wnt signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human bcl9, and we provide genetic and molecular evidence that these... | SIGNOR-116577 |
Q13131 | Q9NYV6 | 1 | phosphorylation | down-regulates | 0.2 | We show that ampk down-regulates rrna synthesis under glucose restriction by phosphorylating the rna polymerase i (pol i)-associated transcription factor tif-ia at a single serine residue (ser-635). | SIGNOR-188403 |
P15498 | Q13588 | 2 | binding | up-regulates | 0.297 | Here we report that both in cell extracts and within intact mammalian cells vav binds to grb2 (sem-5/ash/drk), an adaptor molecule which plays a key role in ras activation. | SIGNOR-33840 |
P40763 | O43683 | 0 | phosphorylation | up-regulates activity | 0.251 | This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.|We further identified through a series of molecular and cell biological approaches that BUB1 interac... | SIGNOR-280198 |
P11229 | P50148 | 2 | binding | up-regulates activity | 0.461 | 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- signali... | SIGNOR-257014 |
P53350 | Q13315 | 0 | phosphorylation | down-regulates activity | 0.429 | Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5\u20137,18] , whereas ATM phosphorylates and inactivates Plk1, consolidating the delay in the entry into M phase [5\u201319] .|Indeed Chk2 mediates the degradation of Cdc25A to activate the S-phase checkpoint [5-7,18], whereas ATM pho... | SIGNOR-279793 |
O15264 | O14733 | 0 | phosphorylation | up-regulates activity | 0.436 | p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation. | SIGNOR-273954 |
Q9Y4C0 | Q14118 | 2 | binding | up-regulates activity | 0.2 | The DGC is potentially recruited to the postsynaptic membrane though a direct neurexin–dystroglycan interaction and an indirect interaction with NL2 via the synaptic scaffolding protein S-SCAM. | SIGNOR-265463 |
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 depl... | SIGNOR-255904 |
Q99708 | P53350 | 0 | phosphorylation | up-regulates activity | 0.347 | PLK1 targets CtIP to promote microhomology mediated end joining.|We further showed that the DSB repair factor CtIP is jointly phosphorylated by CDK1 and Aurora A and PLK1. | SIGNOR-279253 |
P46531 | Q16566 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.36 | In summary, we have found that phosphorylation of Notch1-IC by CaMKIV inhibits the proteasomal degradation of Notch1-IC through Fbw7 ( Fig.\u00a07 ). | SIGNOR-279596 |
Q13009 | Q99835 | 2 | binding | up-regulates | 0.267 | This latter work suggested that inactive smo prevents rac1 activation by interacting with the rac guanine nucleotide exchange factor (gef) t-lymphoma invasion and metastasis 1 (tiam1). This smo-tiam1 complex dissociates upon shh-mediated activation of smo, thus allowing tiam1 to activate rac1 | SIGNOR-199192 |
P61586 | O15085 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.903 | 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... | SIGNOR-260538 |
P31751 | P16220 | 1 | phosphorylation | up-regulates | 0.514 | Creb is a nuclear target for activation via the growth factor-dependent ser/thr kinase akt/pkb. When overexpressed in serum-stimulated cells, akt/pkb potently induced ser-133 phosphorylation of creb and promoted recruitment of cbp. | SIGNOR-62253 |
Q8WZ73 | Q13546 | 1 | ubiquitination | down-regulates quantity by destabilization | 0.468 | We report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitinati... | SIGNOR-271482 |
Q9C0H2 | Q96PU5 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.2 | Our data indicate that Nedd4-2 binds to two family members, TTYH2 and TTYH3, which contain consensus PY ((L/P)PXY) binding sites for HECT type E3 ubiquitin ligases, but not to TTYH1, which lacks this motif. Consistently, Nedd4-2 ubiquitinates both TTYH2 and TTYH3. Importantly, we have shown that endogenous TTYH2 and Ne... | SIGNOR-272633 |
Q13164 | Q02078 | 1 | phosphorylation | up-regulates | 0.711 | We have previously shown that bmk1 regulates c-jun gene expression through direct phosphorylation and activation of transcription factor mef2c.Here, we demonstrate that, in addition to mef2c, bmk1 phosphorylates and activates mef2a and mef2d but not mef2b.The sites phosphorylated by activated bmk1 were mapped to ser-35... | SIGNOR-236579 |
Q15796 | Q15759 | 0 | phosphorylation | down-regulates | 0.352 | Smads can also be phosphorylated in the linker region most prominently by the action of mitogen-activated protein (map) kinaseslinker region phosphorylation can prevent nuclear translocation of smads and inhibit tgf-_ signalling, potentially leading to oncogenesis. | SIGNOR-167848 |
Q8NFG4 | Q9NQL2 | 1 | gtpase-activating protein | up-regulates activity | 0.683 | The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 [..} RagC/D is a key regulator of the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D must be GDP-bound for the interaction to occur | SIGNOR-256504 |
O00327 | P35398 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.689 | Direct Regulation of the NPAS2 Promoter by RORα and REV-ERBα. it appears in the context of the NPAS2 promoter RORα functions as a transcriptional activator, but REV-ERBα may only function as an inhibitor of RORα activity by blocking binding. | SIGNOR-267982 |
Q6ZP65 | O43896 | 2 | binding | up-regulates activity | 0.2 | BICDR-1 interacts with the dynein/dynactin motor complex. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory tra... | SIGNOR-266876 |
Q9UI33 | Q92913 | 2 | binding | down-regulates activity | 0.2 | Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels. | SIGNOR-253435 |
O14965 | O15143 | 1 | phosphorylation | up-regulates activity | 0.46 | Aurora A phosphorylates Arpc1b on threonine 21, and expression of Arpc1b but not a nonphosphorylatable Arpc1b mutant in mammalian cells leads to Aurora A kinase activation and abnormal centrosome amplification in a Pak1-independent manner. | SIGNOR-279438 |
Q6UXX9 | O75473 | 2 | binding | up-regulates | 0.693 | Here we demonstrate that lgr4 and lgr5 bind the r-spondins with high affinity and mediate the potentiation of wnt/betBeta-catenin signaling by enhancing wnt-induced lrp6 phosphorylation | SIGNOR-174532 |
P60880 | Q9ULU8 | 2 | binding | up-regulates activity | 0.368 | CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1 | SIGNOR-264338 |
Q9GZZ7 | O60542 | 2 | binding | up-regulates | 0.747 | Glial cell line-derived neurotrophic factor (gdnf) family ligands signal through receptor complex consisting of a glycosylphosphatidylinositol-linked gdnf family receptor (gfr) alpha subunit and the transmembrane receptor tyrosine kinase ret. | SIGNOR-85162 |
O75030 | Q15418 | 0 | phosphorylation | down-regulates | 0.41 | The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a ... | SIGNOR-174760 |
P25098 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.2 | Phosphorylation of GRK2 by protein kinase C abolishes its inhibition by calmodulin. In vitro, GRK2 was preferentially phosphorylated by PKC isoforms alpha, gamma, and delta. Two-dimensional peptide mapping of PKCalpha-phosphorylated GRK2 showed a single site of phosphorylation, which was identified as serine 29 by HPLC... | SIGNOR-249059 |
Q8TEV9 | Q9Y4P8 | 1 | transcriptional regulation | up-regulates quantity | 0.271 | Global mRNA expression analysis revealed that SMCR8 regulates transcription of several other autophagy genes including WIPI2 | SIGNOR-252028 |
P13385 | P01137 | 2 | binding | down-regulates activity | 0.2 | Ere, we provide evidence supporting a novel mechanism in which Cripto inhibits the tumor suppressor function of TGF-beta. Cripto bound TGF-beta and reduced the association of TGF-beta with its type I receptor, TbetaRI. | SIGNOR-150006 |
P30939 | P63096 | 2 | binding | up-regulates activity | 0.45 | 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- signali... | SIGNOR-256673 |
P45983 | O43524 | 1 | phosphorylation | up-regulates activity | 0.65 | As JNK1 phosphorylates FOXO3 at S574, 12 allowing formation of the proapoptotic species, we tested whether FOXO3 acetylation is required for the JNK1-FOXO3 interaction. | SIGNOR-280030 |
P61006 | O15078 | 2 | binding | up-regulates activity | 0.742 | CEP290 cooperates with Rab8a to promote ciliogenesis and this function is antagonized by CP110. CEP290 recruits Rab8a to centrosomes. Depletion of CEP290 results in a significant decrease of Rab8a at the centrosome and at the cilium, raising the possibility that CEP290 first recruits Rab8a through direct protein-protei... | SIGNOR-252146 |
P16104 | P35226 | 0 | ubiquitination | up-regulates activity | 0.2 | In this process, BMI1 ubiquitinates histone H2A and \u03b3H2AX, thereby facilitating the repair of double-stranded DNA breaks through stimulating homologous recombination and non-homologous end joining. | SIGNOR-278744 |
P07101 | P49137 | 0 | phosphorylation | up-regulates activity | 0.52 | MAPKAP-K2 phosphorylates both Ser19 and Ser40 of TH. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. | SIGNOR-250149 |
P42345 | P06730 | 1 | phosphorylation | down-regulates activity | 0.801 | Mechanistic target of rapamycin complex 1 (mTORC1) phosphorylates and inhibits eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1). | SIGNOR-278963 |
P42226 | P23458 | 0 | phosphorylation | up-regulates activity | 0.765 | IL-4-stimulated Stat6 activation is mediated by Jak1 whereas Tyk2 is required for Stat6 activation in IL-13-treated monocytes | SIGNOR-249531 |
P60321 | P46934 | 0 | ubiquitination | down-regulates quantity by destabilization | 0.2 | We find that NEDD4 targets an RNA-binding protein, NANOS2, in spermatogonia to destabilize it, leading to cell differentiation.|To examine whether complex formation of NEDD4 and NDFIP2 promotes NANOS2 ubiquitination in vivo, FLAG tagged NANOS2 was expressed in HEK293 cells with or without MYC-NEDD4 and MYC-NDFIP2. | SIGNOR-278770 |
P27361 | P08047 | 1 | phosphorylation | up-regulates | 0.653 | We showed that perifosine activates the mitogen-activated protein/extracellular signal-regulated kinase pathway, and this activation promotes the phosphorylation of sp1 in known mitogen-activated protein kinase residues (threonine 453 and 739), thereby leading to increased sp1 binding and enhanced p21(waf1/cip1) transc... | SIGNOR-248062 |
Q9H2K8 | Q13188 | 1 | phosphorylation | up-regulates | 0.291 | In addition, the thousand-and-one (tao) amino acids kinase or taok1 3 has been shown to directly phosphorylate and activate hpo or mst1/2 | SIGNOR-201333 |
P36897 | P84022 | 1 | phosphorylation | up-regulates activity | 0.812 | A major event leading to Smad3 activation is the TGF-beta-induced, TbetaRI-mediated phosphorylation at two C-terminal serine residues, Ser-423 and Ser-425, which triggers dissociation of Smad3 from its receptors to form a complex with Smad4 and accumulate in the nucleus | SIGNOR-235380 |
P10301 | Q9H4L5 | 2 | binding | down-regulates activity | 0.405 | We show that ORP3 interacts with R-Ras, a small GTPase regulating cell adhesion, spreading and migration. Gene silencing of ORP3 in HEK293 cells results in altered organization of the actin cytoskeleton, impaired cell-cell adhesion, enhanced cell spreading and an increase of beta1 integrin activity--effects similar to ... | SIGNOR-277221 |
Q13490 | Q13489 | 2 | binding | up-regulates activity | 0.496 | Ligand-stimulated aggregation of receptor complexes causes recruitment of multiple traf2 trimers, which in turn leads to cIAP1 or cIAP2 dimerization. | SIGNOR-199088 |
P27986 | P42338 | 2 | binding | up-regulates activity | 0.851 | Signal transduction pathways triggered by Tie2 have been extensively examined. Tyr-1101of Tie2 directly associates in a phosphotyrosine (pTyr)-dependent manner with the p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase, which in turn activate PI 3-kinase, leading to cell motility and survival | SIGNOR-242640 |
O75717 | Q13535 | 0 | phosphorylation | up-regulates activity | 0.539 | And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. | SIGNOR-262664 |
Q13535 | Q8N726 | 0 | phosphorylation | up-regulates activity | 0.391 | Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressorInduction of ATR activity in Hs68 E2F1ER cells by endogenous ARF. | SIGNOR-134781 |
P38405 | P29371 | 2 | binding | up-regulates activity | 0.2 | 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- signali... | SIGNOR-256937 |
Q05397 | Q8N1W1 | 1 | phosphorylation | up-regulates activity | 0.459 | Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA ( ).|Importantly, FAK promotes p190RhoGEF tyrosine phosphorylation and enhances activation of RhoA. | SIGNOR-279271 |
P04792 | P31749 | 0 | phosphorylation | down-regulates | 0.66 | First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cell... | SIGNOR-252526 |
P17252 | P06730 | 1 | phosphorylation | up-regulates | 0.382 | Phosphorylation of eIF-4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins.[..] This suggests a two-step model for the phosphorylation (and activation) of eIF4E by growth factors and hormones: first, dissociation of eIF4E . | SIGNOR-248945 |
Q13409 | Q8NG06 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.298 | Trim58 ubiquitinates dynein and promotes its proteasomal degradation. Trim58 binds DIC directly, polyubiquitinates it in vitro, and induces proteasomal degradation of the dynein holocomplex in vivo. | SIGNOR-272841 |
P98170 | P60484 | 1 | ubiquitination | down-regulates quantity | 0.691 | Finally, we found that XIAP can directly ubiquitinate PTEN in vitro.|Overexpression of XIAP induces polyubiquitination of PTEN and proteasome dependent decrease of PTEN protein levels. | SIGNOR-278751 |
Q13315 | Q9NY61 | 1 | phosphorylation | up-regulates quantity by stabilization | 0.355 | The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage. These Che-1 modifications induce a specific recruitment of Che-1 on the TP53 and p21 promoters. |DNA damage stabilizes Che-1 protein|In addition, substitution of Che-1 Ser187 with an a... | SIGNOR-264415 |
P05556 | Q9UN73 | 2 | binding | up-regulates activity | 0.2 | The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. | SIGNOR-265666 |
P08151 | Q92831 | 0 | acetylation | down-regulates activity | 0.469 | NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase | SIGNOR-269270 |
Q92729 | P35222 | 1 | dephosphorylation | down-regulates activity | 0.4 | Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating \u03b2-catenin and reducing the activation of \u03b2-catenin signaling. | SIGNOR-277095 |
Q92585 | P04637 | 2 | binding | up-regulates | 0.31 | Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin). | SIGNOR-180136 |
Q13224 | Q9UQM7 | 0 | phosphorylation | up-regulates activity | 0.7 | By peptide mapping, automated sequencing, and mass spectrometry, we identified the major site of phosphorylation on the fusion protein as Ser-383, corresponding to Ser-1303 of full-length NR2B. The Km for phosphorylation of this site in the fusion protein was approximately 50 nM, much lower than that of other known sub... | SIGNOR-250630 |
O00253 | Q01726 | 2 | binding | down-regulates activity | 0.44 | The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the pro... | SIGNOR-268699 |
O00398 | P63096 | 2 | binding | up-regulates activity | 0.2 | 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- signali... | SIGNOR-256726 |
Q15139 | P19174 | 1 | phosphorylation | down-regulates activity | 0.404 | Thus, phosphorylation of PLC-gamma 1 by PKC or PKA at serine 1248 may modulate the interaction of PLC-gamma 1 with the protein tyrosine kinase or the protein tyrosine phosphatase; this altered interaction may, at least in part, be responsible for the decreased tyrosine phosphorylation of PLC-gamma 1 seen in PMA- and fo... | SIGNOR-248846 |
Q16539 | P35813 | 0 | dephosphorylation | down-regulates activity | 0.408 | Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furtherm... | SIGNOR-59618 |
P48740 | P06681 | 1 | cleavage | up-regulates activity | 0.537 | The MASPs in the preparations had proteolytic activities against C4, C2, and C3 in the fluid phase | SIGNOR-263420 |
P28482 | Q08499-2 | 1 | phosphorylation | down-regulates | 0.353 | The pde4d2 isoform is inhibited by erk2 phosphorylation | SIGNOR-77563 |
P62834 | P52306 | 2 | binding | up-regulates | 0.42 | Smggds has been previously shown to activate a wide variety of small gtpases, including the ras family members rap1a, rap1b, and k-ras, as well as the rho family members cdc42, rac1, rac2, rhoa, and rhob | SIGNOR-171482 |
O95477 | P17612 | 0 | phosphorylation | up-regulates activity | 0.508 | Ser-1042 and Ser-2054, located in the nucleotide binding domains of ABCA1, are major phosphorylation sites for PKA. ABCA1 phosphorylation may affect ApoA-I-dependent phospholipid efflux by either altering the conformation of the protein to a more active state or by affecting the interaction between ABCA1 and its partne... | SIGNOR-250326 |
P36894 | Q9HCE7 | 0 | ubiquitination | down-regulates | 0.66 | Smurf1 and smurf2 are e3 ubiquitin ligases known to suppress tgf-beta signaling through degradation of smads and receptors for tgf-beta and bmps. | SIGNOR-153399 |
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