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 |
|---|---|---|---|---|---|---|---|
P42229 | P24394 | 0 | null | up-regulates | 0.556 | Several cytokine receptors share subchains and targets. For example, the common gamma chain (CGC) is shared by IL2, IL4, IL7, IL9 and IL15 receptors that lead to the activation of STAT5 | SIGNOR-254298 |
O15350 | P06493 | 0 | phosphorylation | down-regulates activity | 0.556 | Cyclin-dependent kinases phosphorylate p73 at threonine 86 in a cell cycle-dependent manner and negatively regulate p73.Furthermore, cyclin a/cdk1/2, cyclin b/cdk1/2, and cyclin e/cdk2 complexes can phosphorylate multiple p73 isoforms in vitro at threonine 86. | SIGNOR-99742 |
P11940 | Q92615 | 0 | binding | up-regulates activity | 0.556 | Here we show that LARP4B is a cytoplasmic protein that co-sediments with polysomes and accumulates upon stress induction in stress granules. Biochemical studies further show that the protein interacts with two key factors of the translational machinery, namely, the cytoplasmic poly(A) binding protein (PABPC1) and the receptor for activated C Kinase (RACK1). The biochemical and functional data of LARP4B presented in this study suggest a possible mode of action of LARP4B in translation. Assuming that LARP4B interacts with mRNA-associated PABPC1 and RACK1 simultaneously, it may form a bridge between the 3′ end of mRNAs and the initiating ribosome. This process would lead to mRNA circularization, possibly in an analogous way as it has been described for PABPC1 and eIF4G, the scaffold protein of the cap-binding complex. | SIGNOR-260940 |
P42224 | P52630 | 0 | binding | up-regulates activity | 0.555 | We then examined STAT2 acetylation within the b-barrel DBD. A direct interaction between the STAT2-DBD (315485) and STAT1 was detected (Figure 6E) (Li et al., 1997). | SIGNOR-217957 |
P42768 | P08631 | 0 | phosphorylation | up-regulates activity | 0.555 | Hck induces tyrosine phosphorylation of WASp. Here we show that the Src family kinase Hck induces phosphorylation of WASp-Tyr(291) independently of Cdc42 and that this causes a shift in the mobility of WASp upon SDS-PAGE. A phospho-mimicking mutant, WASp-Y291E, exhibited an enhanced ability to stimulate actin polymerization in a cell-free system and when microinjected into primary macrophages induced extensive filopodium formation with greater efficiency than wild-type WASp or a Y291F mutant. We propose that phosphorylation of Tyr(291) directly regulates WASp function. | SIGNOR-273957 |
P17947 | P05412 | 0 | binding | up-regulates activity | 0.555 | These results indicate that AML1-ETO competes c-Jun away from binding to the β3β4 domain of PU.1. Thus, the c-Jun coactivation function of PU.1 is down-regulated and this in turn down-regulates transcriptional activity of PU.1. | SIGNOR-255660 |
P63096 | Q92633 | 0 | binding | up-regulates activity | 0.555 | 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-256696 |
P84022 | Q9GZV5 | 0 | binding | up-regulates | 0.555 | Taz has been shown to interact with smad2 and smad3 through its coiled-coil region, and to be important in maintaining the nuclear localization of smad2 and smad3 as well as the expression of their target genes in response to tgf-b signaling and, thus, in the maintenance of human esc self-renewal. | SIGNOR-169841 |
Q02763 | P23467 | 0 | dephosphorylation | down-regulates activity | 0.555 | Simultaneous inhibition of Tie2 cleavage and VE-PTP synergistically enhances Tie2 activation by up to 10-fold (Fig. 7A).|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects .|Tie2 activation is also importantly regulated by vascular endothelial protein tyrosine phosphatase (VE-PTP), which dephosphorylates Tie2 to inhibit its vascular stabilizing effects. | SIGNOR-277059 |
P01137 | P08253 | 0 | cleavage | up-regulates | 0.555 | We also demonstrate that mmp-9, as well as its relative, mmp-2, cleave latent transforming growth factor-beta (tgf-beta), which constitutes a novel mechanism of tgf-beta activation | SIGNOR-74384 |
P27986 | Q05397 | 0 | binding | up-regulates | 0.555 | Pi3-kinase has also been shown to bind fak in a cell cell adhesion-dipendent manner at the major autophosphorylation site y397. This association could live to activation of pi3-kinase and its downstream effectors. | SIGNOR-53979 |
P01584 | Q04206 | 0 | transcriptional regulation | down-regulates activity | 0.555 | Early Inhibition of IL-1 beta Expression by IFN-gamma Is Mediated by Impaired Binding of NF-kappa B to the IL-1 beta Promoter but Is Independent of Nitric Oxide|We report that IFN-γ suppressed bacterial RNA and LPS induced IL-1β transcription in primary murine macrophages | SIGNOR-251736 |
P41597 | P10147 | 0 | binding | up-regulates activity | 0.555 | The purpose of this study was to determine whether certain chemokines, which are highly expressed in injured skeletal muscle, are involved in the repair and functional recovery of the muscle after traumatic injury. In wild-type control mice, mRNA transcripts of macrophage inflammatory protein (MIP)-1, MIP-1, and monocyte chemoattractant protein (MCP)-1 as well as their major receptors, CCR5 and CCR2, increased after freeze injury and gradu- ally returned to control (uninjured) levels by 14 days. | SIGNOR-251723 |
Q04206 | Q05513 | 0 | phosphorylation | up-regulates | 0.555 | Rela is phosphorylated at: ser276 by the catalytic subunit of protein kinase a (pkac), msk1 and msk2; at ser311 by the atypical pkczeta; at ser468 by ikkbeta, ikkepsilon and glycogen-synthase kinase-3beta (gsk3beta); at ser529 by ck2; and at ser536 by ikkbeta, ikkalfa, ikkepsilon, nf-kb activating kinase (nak, also known as tank-binding kinase-1 tbk1)) and rsk1 (also known as p90 ribosomal protein s6 kinase (p90s6k) | SIGNOR-151432 |
Q00535 | P48730 | 0 | phosphorylation | up-regulates activity | 0.555 | We also show that casein kinase I, but not casein kinase II, can phosphorylate and activate cdk5 in vitro. | SIGNOR-250798 |
P51828 | Q05655 | 0 | phosphorylation | up-regulates activity | 0.555 | Immunoprecipitation data indicated that PKCdelta could bind and directly phosphorylate AC7. | SIGNOR-279258 |
Q9NQB0 | Q9UKE5 | 0 | phosphorylation | up-regulates | 0.555 | Here, we report that tnik is an activating kinase for tcf4 and essential for colorectal cancer growth. Tnik, but not its catalytically inactive mutant, phosphorylated the conserved serine 154 residue of tcf4. | SIGNOR-165946 |
Q03181 | P28702 | 0 | binding | up-regulates | 0.555 | Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology | SIGNOR-105451 |
Q9UBK2 | P16220 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.554 | CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo | SIGNOR-256150 |
P60953 | O14827 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.554 | 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-260575 |
Q00722 | P62873 | 0 | binding | up-regulates | 0.554 | Activation of plc-beta 2 by beta gamma subunits may be an important mechanism by which pertussis toxin-sensitive g proteins stimulate plc. | SIGNOR-19447 |
O14757 | P24941 | 0 | phosphorylation | up-regulates | 0.554 | Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency | SIGNOR-175083 |
P62993 | Q7L591 | 0 | binding | up-regulates activity | 0.554 | An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling. | SIGNOR-268448 |
Q08881 | P06239 | 0 | phosphorylation | up-regulates | 0.554 | Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity. The major site of Lck phosphorylation on Itk was mapped to the conserved tyrosine (Tyr511) in the activation loop of the Itk kinase domain. | SIGNOR-251380 |
P10398 | Q6VAB6 | 0 | binding | up-regulates activity | 0.553 | In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK).Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. | SIGNOR-273875 |
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 |
Q92558 | O43295 | 0 | binding | up-regulates | 0.553 | Wrp binds directly to wave-1 through its src homology domain 3 and specifically inhibits rac function in vivo. | SIGNOR-95967 |
P02686 | P28482 | 0 | phosphorylation | down-regulates | 0.553 | Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The identification of myelin basic protein (phosphorylation at -pro-arg-thr-pro-) as a substrate for the erk kinases (fig. 1) demonstrates that there are other determinants important for substrate recognition than those present in the originally identified consensus sequence. | SIGNOR-22420 |
P46527 | P07948 | 0 | phosphorylation | down-regulates | 0.553 | We previously reported that y88 phosphorylation of p27(kip1) by oncogenic tyrosine kinases impairs p27(kip1)-mediated cdk inhibition, and initiates its ubiquitin-dependent proteasomal degradation. | SIGNOR-172904 |
Q04771 | Q16671 | 0 | binding | up-regulates | 0.553 | See table2 | SIGNOR-121593 |
P61586 | O14827 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.553 | 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-260573 |
P14598 | P17252 | 0 | phosphorylation | up-regulates | 0.553 | Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation. | SIGNOR-89178 |
O43318 | Q13546 | 0 | binding | up-regulates activity | 0.553 | RIP-1 recruitment of MEKK-3 and transforming growth factor-beta (TGFbeta)-activated kinase (TAK1) subsequently activates the IKK (inhibitor of κB kinase) complex | SIGNOR-256022 |
P04150 | Q8IZL8 | 0 | transcriptional regulation | up-regulates quantity by expression | 0.553 | MNAR functionally interacts with both NH2- and COOH-terminal GR domains to modulate transactivation | SIGNOR-251681 |
Q05397 | P09619 | 0 | phosphorylation | up-regulates | 0.553 | In this study, we demonstrate that growth factor receptors including hepatocyte growth factor receptor met, epidermal growth factor receptor, and platelet-derived growth factor receptor directly phosphorylate fak on tyr194 in the ferm domain collectively, this study provides the first example to explain how fak is activated by receptor tyrosine kinases. | SIGNOR-167658 |
Q9NR61 | Q86YT6 | 0 | ubiquitination | up-regulates activity | 0.553 | Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity. | SIGNOR-209626 |
Q9NQW1 | Q53G59 | 0 | binding | up-regulates activity | 0.553 | By analyzing mouse embryonic stem cell (mESC) division, we have identified Cul3Klhl12 as a regulator of COPII coat formation. Cul3Klhl12 monoubiquitinates Sec31 and drives assembly of large COPII-coats. As a result, ubiquitination by Cul3Klhl12 is essential for collagen export, a step that is required for integrin-dependent mESC division. | SIGNOR-272014 |
P12004 | Q149N8 | 0 | ubiquitination | up-regulates | 0.553 | We provide evidence that similar to rad5, shprh physically interacts with the human rad6rad18 and mms2ubc13 protein complexes, and importantly, we show that it exhibits an ubiquitin ligase activity and mediates mms2ubc13-dependent polyubiquitylation of pcna. Thus, shprh is a functional homolog of rad5. | SIGNOR-187757 |
Q9Y253 | P51587 | 0 | binding | up-regulates | 0.553 | Palb2 and brca2 interact with pol_ and are required to sustain the recruitment of pol_ at blocked replication forks. Palb2 and brca2 stimulate pol_-dependent dna synthesis on d loop substrates | SIGNOR-204538 |
Q96J02 | Q9Y3C5 | 0 | binding | up-regulates activity | 0.553 | Rnf11, together with tax1bp1 and itch, is an essential component of an a20 ubiquitin-editing protein complex; rnf11 is required for a20 to interact with and inactivate rip1 to inhibit tnf-mediated nf-_kb activation. | SIGNOR-183188 |
P50148 | P41595 | 0 | binding | up-regulates activity | 0.553 | 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-257138 |
P02751 | P02679 | 0 | binding | down-regulates activity | 0.553 | Fibrinogen y-chain carboxyterminal (GQQHHLGGAKQAGDV) peptides inhibit fibrinogen, fibronectin (Fn), vitronectin, and von Willebrand factor (vWF) binding to the platelet glycoprotein Ilb-Illa complex (GP lIbII1a). | SIGNOR-251970 |
P23528 | P12931 | 0 | phosphorylation | down-regulates | 0.553 | Tyrosine phosphorylation of cofilin at y68 by v-src leads to its degradation through ubiquitin-proteasome pathway | SIGNOR-188352 |
P11831 | P68400 | 0 | phosphorylation | up-regulates activity | 0.552 | Casein kinase II (CKII) phosphorylates the mammalian transcription factor serum response factor (SRF) on a serine residue(s) located within a region of the protein spanning amino acids 70 to 92, thereby enhancing its DNA-binding activity in vitro.| Nevertheless, additional mutation of serines 77 and 79 was required before phosphorylation and enhanced binding were completely abolished. Thus, serines 77 and 79 could also be recognized by CKII if serines 83 and 85 were mutated. | SIGNOR-250955 |
P10415 | P28482 | 0 | phosphorylation | up-regulates quantity by stabilization | 0.552 | Phosphorylation of the map kinase sites in bcl-2, thr56, thr74, and ser87, is sufficient to inhibit tnf--induced degradation. | SIGNOR-74931 |
P46531 | P49336 | 0 | phosphorylation | down-regulates | 0.552 | Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo. | SIGNOR-130640 |
P40763 | P43405 | 0 | phosphorylation | up-regulates activity | 0.552 | The current study indicates that the plasma cell malignancy is also associated with Syk-activated STAT3 directly downstream of reelin-induced integrin \u03b21 engagement and FAK/Src activation (Figure xref ).|The integrin-activated spleen tyrosine kinase (Syk) was shown to promote STAT3 phosphorylation [42, 44]. | SIGNOR-279298 |
P50148 | P30559 | 0 | binding | up-regulates activity | 0.552 | OT binds to its cognate G protein–coupled receptor (OTR) and exerts diverse effects, including stimulation (Gs) or inhibition (Gi/o) of adenylyl cyclase, stimulation of potassium channel currents (Gi), and activation of phospholipase C (Gq). | SIGNOR-270332 |
P03372 | Q01851 | 0 | binding | up-regulates activity | 0.552 | The POU domain of Brn-3a and Brn-3b was shown to interact with the DNA-binding domain of the ER. Brn-3-ER interactions also affect transcriptional activity of an ERE-containing promoter, such that in estradiol-stimulated cells, Brn-3b strongly activated the promoter via the ERE, while Brn-3a had a mild inhibitory effect. | SIGNOR-241275 |
P40763 | P18031 | 0 | dephosphorylation | down-regulates activity | 0.552 | PTP1B was able to dephosphorylate activated JAK2 and STAT3 in vitro, whereas either no or a minimal effect was observed with cluster of differentiation 45 (CD45), PTPalpha and leukocyte antigen-related (LAR). By utilisation of a selective PTP1B inhibitor, the leptin-induced STAT3 activation was enhanced in cells. In conclusion, these results suggested that the negative regulatory role of PTP1B on leptin signalling is mediated through a direct and selective dephosphorylation of the two signalling molecules, JAK2 and STAT3. | SIGNOR-248427 |
P78314 | P43405 | 0 | phosphorylation | up-regulates activity | 0.552 | By using the transient expression system in COS-7 cells, we have demonstrated that 3BP2 was predominantly phosphorylated on Tyr174, Tyr183, and Tyr446 when it was coexpressed with Syk. | SIGNOR-246596 |
Q08828 | P63096 | 0 | binding | down-regulates activity | 0.552 | GTP-bound, active WT Gαi1 acts to inhibit AC, resulting in a decreased concentration of intracellular cAMP. | SIGNOR-256498 |
P46695 | P28482 | 0 | phosphorylation | up-regulates | 0.552 | Upon phosphorylation by erks, iex-1 acquires the ability to inhibit cell death induced by various stimuli. In turn, iex-1 potentiates erk activation in response to various growth factors. | SIGNOR-93740 |
Q14160 | Q05086 | 0 | polyubiquitination | down-regulates quantity by destabilization | 0.552 | Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase | SIGNOR-272573 |
P36894 | Q9HAU4 | 0 | ubiquitination | down-regulates | 0.552 | 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-192898 |
P16885 | P08631 | 0 | phosphorylation | up-regulates activity | 0.552 | The phosphorylation of purified phospholipase C-gamma 1 (PLC-gamma 1) and PLC-gamma 2 by src-family-protein tyrosine kinases (PTKs) P56lck, p53/56lyn, p59hck, p59fyn, and p60src was studied in vitro. All five PTKs phosphorylated PLC-gamma 1 and PLC-gamma 2, suggesting that both PLC-gamma isozymes can be phosphorylated in cells by any of the src-family PTKs in response to the activation of cell surface receptors. | SIGNOR-249364 |
Q05397 | P09769 | 0 | phosphorylation | up-regulates | 0.552 | Phosphorylated on tyrosine residues upon activation. Phosphorylation at tyr-925 is important for interaction with grb2 and depends on the complex formation between fak and the src-kinase fgr. | SIGNOR-94405 |
P53350 | Q13153 | 0 | phosphorylation | up-regulates | 0.552 | We show here that pak1 is required for cell proliferation, mitotic progression and plk1 activity in hela cells. phosphorylation of plk1 on ser 49 is important for metaphase-associated events. | SIGNOR-178353 |
P22415 | Q16539 | 0 | phosphorylation | up-regulates activity | 0.552 | Following uv irradiation, usf-1 is phosphorylated by the p38 stress-activated kinase on threonine 153 and directly up-regulates expression of the pomc, mc1r, tyr, tyrp-1 and dct genes | SIGNOR-185572 |
O75581 | P48729 | 0 | phosphorylation | up-regulates | 0.552 | We show that wnt induces sequential phosphorylation of lrp6 by gsk3 and casein kinase 1, and this dual phosphorylation promotes the engagement of lrp6 with the scaffolding protein axin.Site ii, like site i, was phosphorylated, as detected by means of a phospho-specific antibody (ab1493, for phosphorylated t1493 in lrp6) | SIGNOR-143034 |
Q9BVI0 | P31749 | 0 | phosphorylation | down-regulates | 0.552 | Akt phosphorylates phf20 at ser(291) in vitro and in vivo, which results in its translocation from the nucleus to the cytoplasm and attenuation of phf20 function. | SIGNOR-252529 |
Q16584 | Q9UPT6 | 0 | binding | up-regulates | 0.552 | These data demonstrate that jip3 interacts with proteins that can form a mapk signaling module, including jnk, mkk7, and mlk3jip3 increases mlk3-stimulated jnk activity. | SIGNOR-73909 |
Q92843 | Q9BXH1 | 0 | binding | down-regulates | 0.552 | Only bimbh3 and bbc3 had comparable strong affinitiesfor all the prosurvival proteins. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1. | SIGNOR-133814 |
P61586 | Q52LW3 | 0 | gtpase-activating protein | down-regulates activity | 0.552 | 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-260484 |
Q96HS1 | Q14145 | 0 | binding | down-regulates quantity by destabilization | 0.552 | Keap1-dependent ubiquitination of PGAM5 results in proteasome-dependent degradation of PGAM5. Keap1 is a Bric-a-Brac (BTB) 2 -Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex. | SIGNOR-272645 |
Q92574 | P54646 | 0 | phosphorylation | up-regulates | 0.551 | Under energy starvation conditions, the amp-activated protein kinase (ampk) phosphorylates tsc2 and enhances its activity. | SIGNOR-119541 |
Q96EB6 | P42345 | 0 | phosphorylation | down-regulates activity | 0.551 | These results demonstrate that the inhibition of SIRT1 by mTOR fosters survival of DNA damage-induced prematurely senescent squamous cell carcinoma cells via Bfl-1/A1 in the absence of functional p53.|This process involved the mTOR-dependent phosphorylation of SIRT1 at serine 47, resulting in the inhibition of the deacetylase activity of SIRT1. | SIGNOR-280047 |
P55072 | Q96JH7 | 0 | binding | up-regulates activity | 0.551 | Golgi biogenesis requires two distinct p97ATPase-mediated membrane fusion, the p97/p47 and p97/p37 pathways. |We clarified that VCIP135, an essential factor in both p97 membrane fusion pathways, is phosphorylated on Threonine-760 and Serine-767 by Cdc2 at mitosis and that this phosphorylated VCIP135 does not bind to p97. | SIGNOR-265039 |
P26038 | Q5S007 | 0 | phosphorylation | up-regulates activity | 0.551 | This led to the discovery that moesin, a protein which anchors the actin cytoskeleton to the plasma membrane, is efficiently phosphorylated by lrrk2, at thr558. Moesin phosphorylation could be essential to support the cytoskeletal changes accompanying this process. | SIGNOR-154498 |
Q9BV73 | Q15154 | 0 | relocalization | up-regulates | 0.551 | Recruitment of nek2 and c-nap1 to the centrosome is dependent on pcm-1 | SIGNOR-133334 |
P08151 | P17612 | 0 | phosphorylation | down-regulates | 0.551 | We report that activation of PKA retains Gli1 in the cytoplasm. Conversely, inhibition of PKA activity promotes nuclear accumulation of Gli1.We provide direct evidence to support that the cAMP/PKA signaling axis regulates Gli1 protein localization primarily through a site at Thr374. .These data suggest that Thr374 is an important PKA site responsible for PKA phosphorylation and for the transcriptional activity of Gli1. | SIGNOR-253539 |
Q9C0C7 | P63167 | 0 | binding | down-regulates | 0.551 | The beclin 1vps34 complex is tethered to the cytoskeleton through an interaction between the beclin 1interacting protein ambra1 and dynein light chains 1/2. | SIGNOR-168255 |
O43318 | O75688 | 0 | dephosphorylation | down-regulates activity | 0.551 | In vitro, PP2Cbeta-1 dephosphorylated and inactivated TAK1. | SIGNOR-277154 |
Q99081 | Q02363 | 0 | binding | down-regulates activity | 0.551 | All three Ids bound with high affinity to E proteins .Each Id was able to disrupt the ability of E protein-MyoD complexes to transactivate from a muscle creatine kinase reporter construct in vivo. | SIGNOR-241131 |
P35222 | Q86UP0 | 0 | binding | up-regulates activity | 0.551 | At its C-terminus, cadherin interacts with β-catenin, which dynamically associates with α-catenin, a direct binding partner of filamentous actin | SIGNOR-265862 |
Q05397 | P51813 | 0 | phosphorylation | up-regulates | 0.551 | Bmx phosphorylated focal adhesion kinase (fak) at tyr577 subsequent to its src-mediated phosphorylation at tyr576. Loss of bmx by rna interference or by genetic deletion in mouse embryonic fibroblasts (mefs) markedly impaired fak activity. | SIGNOR-202139 |
P50750 | P50613 | 0 | phosphorylation | up-regulates activity | 0.551 | Cdk7 activates Cdk9 in vitro .|Cdk7 phosphorylates wild-type Cdk9 on Thr186, resulting in increased activity towards a recombinant GST-Spt5 substrate. | SIGNOR-279455 |
P02741 | P08603 | 0 | binding | down-regulates activity | 0.551 | In this study, we provide mechanistic insight into how CRP contributes to the development of AMD. In particular, we show that monomeric CRP (mCRP) but not the pentameric form (pCRP) upregulates IL-8 and CCL2 levels in retinal pigment epithelial cells. Further, we show that complement factor H (FH) binds mCRP to dampen its proinflammatory activity. FH from AMD patients carrying the “risk” His402 polymorphism displays impaired binding to mCRP, and therefore proinflammatory effects of mCRP remain unrestrained. | SIGNOR-252145 |
P29350 | P06241 | 0 | phosphorylation | up-regulates activity | 0.551 | By contrast, receptor multivalent aggregation induced a Fyn-dependent SHP-1 S591 phosphorylation (Fig.\u00a0 xref ).|Fyn simultaneously activates the PI3K-PKC\u03b1 pathway, leading to SHP-1 phosphorylation on serine 591. | SIGNOR-279716 |
Q9BXL7 | O15530 | 0 | phosphorylation | up-regulates | 0.55 | We demonstrate that 3-phosphoinositide-dependent kinase 1 (pdk1) has an essential role in this pathway by regulating the activation of pkc and through signal-dependent recruiting of both pkc and card11 to lipid rafts. | SIGNOR-134866 |
P15056 | Q92963 | 0 | binding | up-regulates activity | 0.55 | It is possible that RIT1 interacts with RAF1 and that gain-of-function mutations in RIT1 and RAF1 exert similar effects in heart development. | SIGNOR-251650 |
P54845 | Q96SL8 | 0 | binding | up-regulates activity | 0.55 | Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells. | SIGNOR-223796 |
P84022 | P35658 | 0 | binding | up-regulates | 0.55 | We demonstrate that smad3 and smad4 are capable of interaction with the nucleoporin can/nup214, and this interaction is required for nuclear import. | SIGNOR-117644 |
Q14790 | Q16539 | 0 | phosphorylation | down-regulates | 0.55 | P38-mapk can directly phosphorylate and inhibit the activities of caspase-8 | SIGNOR-122103 |
Q9Y496 | P49407 | 0 | binding | up-regulates | 0.55 | Kif3a is essential for shh-mediated signaling in mammalian systems (5), and we identified kif3a as a arr1 binding partner in a proteomics screen (18). To test whether arrs, smo, and kif3a might work in concert. | SIGNOR-178672 |
O00401 | P00519 | 0 | phosphorylation | up-regulates activity | 0.55 | Abl phosphorylates N-WASP on tyrosines 175 and 256. Phosphorylation at this site stabilizes the active conformation of N-WASP, resulting in comet tail elongation. | SIGNOR-251437 |
P16284 | P41240 | 0 | phosphorylation | up-regulates activity | 0.55 | We demonstrated that phosphorylation of PECAM-1 by Src or Csk family kinases was sufficient to trigger its association with SHP-2. Moreover, it was able to promote binding of PECAM-1 to SHP-1, a SHP-2-related protein-tyrosine phosphatase expressed in hemopoietic cells. Taken together, these findings indicated that the Src and Csk families of kinases are strong candidates for mediating tyrosine phosphorylation of PECAM-1 and triggering its association with SH2 domain-containing phosphatases under physiological circumstances. | SIGNOR-262741 |
O15379 | P15976 | 0 | relocalization | up-regulates activity | 0.55 | GATA1 is a new substrate of p21-activated kinase 5 (PAK5), which is phosphorylated on serine 161 and 187 (S161 and S187). GATA1 recruits HDAC3/4 to E-cadherin promoter, which is reduced by GATA1 S161A S187A mutant. These data indicate that phosphorylated GATA1 recruits more HDAC3/4 to promote transcriptional repression of E-cadherin, leading to the EMT of breast cancer cells. | SIGNOR-275664 |
Q9UQL6 | Q6W2J9 | 0 | binding | up-regulates activity | 0.55 | BCoR can interact w Because HDACs appear to be involved in repression by an increasing number of transcriptional repressors, we tested whether BCoR can associate with HDACs. BCoR can interact with HDAC1, HDAC3, and HDAC-B/5 more strongly than with HDAC-A/4, HDAC-C, HDAC-D, and HDAC-E. | SIGNOR-252238 |
P33032 | O00253 | 0 | binding | down-regulates activity | 0.55 | 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 proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins | SIGNOR-268714 |
Q15717 | O96017 | 0 | phosphorylation | down-regulates activity | 0.55 | Given the fact that Chk2 phosphorylates HuR at residues S88, S100 and T118 and that each individual phosphorylation site by Chk2 plays a distinct role in regulating HuR- binding to different target mRNAs (22,42), we further tested HuR mutants with alanine substitutions at each of the Chk2 phosphorylation sites. | SIGNOR-278163 |
P46531 | Q9NWT6 | 0 | hydroxylation | down-regulates | 0.55 | We show that fih-1 hydroxylates notch icd at two residues (n(1945) and n(2012)) that are critical for the function of notch icd as a transactivator within cells and during neurogenesis and myogenesis in vivo. Fih-1 negatively regulates notch activity and accelerates myogenic differentiation. | SIGNOR-161057 |
P40763 | P51617 | 0 | phosphorylation | up-regulates | 0.55 | Irak1 can directly use stat3 as a substrate and cause stat3 serine 727 phosphorylation. | SIGNOR-129685 |
Q14118 | P12931 | 0 | phosphorylation | down-regulates | 0.55 | Tyrosine 892 is now thought to be the principal site for recognition by the c-src tyrosine kinase;. We show that upon tyrosine phosphorylation, beta-dystroglycan undergoes a profound change in its sub-cellular localization (e.g., from the plasma membrane to an internal membrane compartment). One possibility is that the net negative charge at position 892 causes the redistribution of beta-dystroglycan to this intracellular vesicular location | SIGNOR-101655 |
O14983 | O00631 | 0 | binding | down-regulates activity | 0.55 | These results suggest that sAnk1 interacts with SLN both directly and in complex with SERCA1 and reduces SLN's inhibitory effect on SERCA1 activity. | SIGNOR-265929 |
P11217 | P15735 | 0 | phosphorylation | up-regulates activity | 0.55 | It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15 | SIGNOR-267400 |
Q92831 | P04150 | 0 | relocalization | up-regulates activity | 0.549 | NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase | SIGNOR-269233 |
P61586 | Q96PE2 | 0 | guanine nucleotide exchange factor | up-regulates activity | 0.549 | 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-260542 |
Q15796 | P29590 | 0 | binding | up-regulates activity | 0.549 | Cytoplasmic pml physically interacts with smad2/3 and sara (smad anchor for receptor activation) and is required for association of smad2/3 with sara and for the accumulation of sara and tgf-beta receptor in the early endosome. | SIGNOR-128738 |
Q15796 | Q9UQM7 | 0 | phosphorylation | down-regulates | 0.549 | Smad2 is a target substrate for cam kinase ii in vitro at serine-110, -240, and -260. furthermore, cam kinase ii blocked nuclear accumulation of a smad2 and induced smad2-smad4 hetero-oligomerization independently of tgfbeta receptor activation, while preventing tgfbeta-dependent smad2-smad3 interactions. | SIGNOR-82970 |
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