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14
P24941
Q5MJ70
0
relocalization
up-regulates activity
0.791
Speedy/RINGO A, a noncanonical activator of CDK2, was recently identified as a key regulator for CDK2 recruitment to meiotic telomeres
SIGNOR-263310
Q9GZV5
O95835
0
phosphorylation
down-regulates
0.791
In response to high cell densities, activated LATS1/2 phosphorylates the WW-domain containing transcriptional co-activators YAP at Ser127 and TAZ at Ser89, promoting 14-3-3 binding and thereby inhibiting their translocation into the nucleus.
SIGNOR-197643
Q9Y6C5
Q14623
0
binding
down-regulates activity
0.791
Biochemical analysis of ptch and ptch2 shows that they both bind to all hedgehog family members with similar affinity and that they can form a complex with smo.Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven-transmembrane-protein Smoothened (SMO) by PTCH.
SIGNOR-61314
P98155
P78509
0
binding
up-regulates
0.791
The hypothesis that the vldl receptor signals in response to reelin binding was recently supported by studies (37) showing direct binding of reelin to the vldl receptor and changes in tyrosine phosphorylation in response to reelin-vldl receptor association.
SIGNOR-106295
Q13546
Q13158
0
binding
up-regulates activity
0.791
Rip1 is required for the formation of a rip1/fadd/caspase-8 complex that drives caspase-8 activation, cleavage of bid into tbid, mitochondrial outer membrane permeabilization, full activation of caspase-3 and caspase-dependent apoptosis. Tweak induces assembly of a death-signaling complex containing rip1, fadd, and caspase-8
SIGNOR-191781
P51003
Q6UN15
0
binding
up-regulates
0.791
Recombinant hfip1 is sufficient to stimulate the in vitro polyadenylation activity of pap in a u-rich element-dependent manner. hfip1, cpsf160 and pap form a ternary complex in vitro, suggesting that hfip1 and cpsf160 act together in poly(a) site recognition and in cooperative recruitment of pap to the rna.
SIGNOR-121700
P42224
P23458
0
phosphorylation
up-regulates activity
0.79
The central event in cytokine_dependent transcriptional regulation is phosphorylation of STATs on a single tyrosine residue at their C_terminus (Darnell, 1997b). The reaction is catalyzed by cytokine receptor_associated tyrosine kinases of the Janus type (Jak) at the cell membrane and triggers the homo_ and heterodimerization of STAT molecules via reciprocal phosphotyrosine“SH2 domain interactions
SIGNOR-236373
P40189
P15018
0
binding
up-regulates
0.79
Stimulation of cells with the interleukin-6 family of cytokines triggers homo- or hetero-dimerization of gp130. The dimerization of gp130 leads to activation of associated cytoplasmic tyrosine kinases and subsequent modification of transcription factors.Some Of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-2
SIGNOR-48108
O75581
P56704
0
binding
up-regulates activity
0.79
Here, we present evidence that lrp6 is internalized with caveolin and that the components of this endocytic pathway are required not only for wnt-3a-induced internalization of lrp6 but also for accumulation of beta-catenin.
SIGNOR-148671
P05412
P28482
0
phosphorylation
up-regulates activity
0.79
Erk also undergoes rapid translocation into the nucleus, where it phosphorylates and activates a variety of transcription factor targets, including sp1, e2f, elk-1, and ap1.
SIGNOR-201943
Q96CW1
Q2M2I8
0
phosphorylation
up-regulates
0.79
Aak1 is enriched at presynaptic terminals, whereas in nonneuronal cells it colocalizes with clathrin and ap2 in clathrin-coated pits and at the leading edge of migrating cells. Aak1 specifically phosphorylates the mu subunit in vitro, and stage-specific assays for endocytosis show that mu phosphorylation by aak1 results in a decrease in ap2-stimulated transferrin internalization. Together, these results provide strong evidence that aak1 is the endogenous mu 2 kinase and plays a regulatory role in clathrin-mediated endocytosis.
SIGNOR-115657
P13498
P14598
0
binding
up-regulates activity
0.79
Stimulus-induced phosphorylation of p47phox causes a conformational change, by which both PX and SH3 domains become accessible to their membranous targets, phosphoinositides and p22phox, respectively. Cooperation of these two interactions, each being indispensable, enables p47phox to form a stable complex with cytochrome b558 (composed of the two subunit gp91phox and p22phox), leading to activation of the phagocyte NADPH oxidase.
SIGNOR-276625
Q9UM47
Q92585
0
binding
up-regulates
0.79
Maml1 binds to the ankyrin repeat domain of all four mammalian notch receptors, forms a dna-binding complex with icn and rbp-jkappa, and amplifies notch-induced transcription of hes1.
SIGNOR-84838
Q13153
P63000
0
binding
up-regulates activity
0.79
A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways.
SIGNOR-248236
P35222
O95996
0
relocalization
down-regulates quantity by destabilization
0.79
The tumour-suppressing activity of apc largely involves facilitating the proteasome-mediated degradation of b-cateninit is possible that once exported from the nucleus, apc directs b-catenin along the cytoskeletal network to sites of degradation.
SIGNOR-81545
P01112
Q07890
0
guanine nucleotide exchange factor
up-regulates
0.79
Grb2 binds and activates sos, which then activates ras, and this activates p110 independently of p85.
SIGNOR-175262
Q13501
Q9H0R8
0
binding
up-regulates activity
0.79
P62 binds both to lc3a and -b and the related gabarap family proteins/this interaction is necessary for autophagic degradation of p62-positive cytoplasmic inclusion bodies containing ubiquitinated proteins. We also demonstrate that alis are indistinguisha
SIGNOR-156304
Q9BQ95
Q9Y4K3
0
ubiquitination
down-regulates activity
0.79
Here we demonstrate that engagement of a subset of Toll-like receptors (TLR1, TLR2 and TLR4) results in the recruitment of mitochondria to macrophage phagosomes and augments mROS production. This response involves translocation of a TLR signalling adaptor, tumour necrosis factor receptor-associated factor 6 (TRAF6), to mitochondria, where it engages the protein ECSIT (evolutionarily conserved signalling intermediate in Toll pathways), which is implicated in mitochondrial respiratory chain assembly. Interaction with TRAF6 leads to ECSIT ubiquitination and enrichment at the mitochondrial periphery, resulting in increased mitochondrial and cellular ROS generation
SIGNOR-260370
P24928
P50613
0
phosphorylation
down-regulates
0.789
Although there is some inconsistency in the literature, it is generally thought that cdk7, a component of the transcription factor (tf) iih, is a major ser-5 kinase, whereas cdk9, a component of positive transcription elongation factor (p-tef) b, is a major ser-2 kinase within cells. These results suggest that subsequent to h2o2 treatment, the ser-5-phosphorylated form, but not the ser-2-phosphorylated form or the unphosphorylated form, is targeted for rapid proteasomal degradation through its ubiquitination.
SIGNOR-120024
Q02750
P15056
0
phosphorylation
up-regulates activity
0.789
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residueserine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf.
SIGNOR-235475
Q14315
Q8WUP2
0
binding
up-regulates activity
0.789
Kindlin binds migfilin tandem LIM domains and regulates migfilin focal adhesion localization and recruitment dynamics. Two integrin-binding proteins present in FAs, kindlin-1 and kindlin-2, are important for integrin activation, FA formation, and signaling. By binding filamin, migfilin provides a link between kindlin and the actin cytoskeleton.
SIGNOR-266107
P40763
P12931
0
phosphorylation
up-regulates activity
0.789
In the present study, we have delineated the mechanism by which Galpha16 stimulates STAT3 in human embryonic kidney 293 cells. A constitutively active Galpha16 mutant, Galpha16QL, stimulated STAT3-dependent luciferase activity as well as the phosphorylation of STAT3 at both Tyr705 and Ser727.The involvement of tyrosine kinases such as c-Src and Janus kinase 2 and 3 (JAK2 and JAK3) in Galpha16QL-induced activation of STAT3 was illustrated by the combined use of selective inhibitors and dominant negative mutants.
SIGNOR-247341
Q9BXW9
Q13315
0
phosphorylation
up-regulates
0.789
These results suggest that s222 and either s1401, s1404, or s1408 are sites of atm-dependent phosphorylation in vitro.Phosphorylation Of fancd2 is required for activation of an s phase checkpoint
SIGNOR-90117
P36897
O15105
0
binding
down-regulates activity
0.789
SMAD7 functions as an antagonist to TGFB by binding to the TBRI and thus inhibiting activation of SMAD2 and SMAD3.
SIGNOR-64088
Q9Y4K3
Q9NQC7
0
deubiquitination
down-regulates
0.789
The nf-kappab activation by cyld is mediated, at least in part, by the deubiquitination and inactivation of tnfr-associated factor 2 (traf2) and, to a lesser extent, traf6.
SIGNOR-117856
P45983
P28562
0
dephosphorylation
down-regulates
0.789
Jnk1 phosphorylation and activation was inhibited by expression of both mkp1 and mkp2.
SIGNOR-46079
P62834
Q9Y4G8
0
guanine nucleotide exchange factor
up-regulates activity
0.789
Our data are consistent with a pathway involving the cAMP-mediated activation of Rapgef2, which then stimulates Rap1, leading to increases in B-Raf, MEK, and ERK activity.Increased intracellular concentrations of cAMP enhanced the Rapgef2-dependent activation of Rap1, which in turn associated with B-Raf to enable the activation of ERK and subsequent neuronal- and endocrine-specific cellular outcomes, such as induction of neuroendocrine-specific genes and extension of neuritic processes (neuritogenesis).
SIGNOR-276609
P52630
P29597
0
phosphorylation
up-regulates activity
0.789
JAK1 and TYK2 will phosphorylate and activate STAT1 and STAT2 respectively, leading to the formation of the ternary interferon-stimulated gene factor 3 (ISGF3) complex, composed of STAT1, STAT2 and interferon regulatory factor 9 (IRF9).
SIGNOR-279133
P21333
Q13153
0
phosphorylation
up-regulates
0.789
In flna, the pak1-binding site involves tandem repeat 23 in the carboxyl terminus and phosphorylation takes place on serine 2152.
SIGNOR-92065
O15169
Q5JTC6
0
relocalization
up-regulates activity
0.789
Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.
SIGNOR-171886
Q9BXW4
O95352
0
binding
up-regulates activity
0.789
Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe
SIGNOR-191540
P38398
Q92878
0
binding
up-regulates
0.789
Brca1 interacts in vitro and in vivo with hrad50. Brca1 is important for the cellular responses to dna damage that are mediated by the hrad50-hmre11-p95 complex.
SIGNOR-69701
P00451
P04275
0
binding
up-regulates activity
0.789
Binding of FVIII to VWF is needed to maintain appropriate plasma levels, as FVIII plasma levels and half-life are remarkably reduced in the absence of VWF
SIGNOR-251967
P13639
O00418
0
phosphorylation
down-regulates
0.788
Ef-2 kinase phosphorylates ef-2 at 3 threonine residues: thr-53, thr-56, thr-58. Phosphorylation of thr56 and thr58 was found to be an ordered process, modification of thr56 preceding, and apparently being required for, phosphorylation of thr58.
SIGNOR-38556
P35568
P23443
0
phosphorylation
down-regulates quantity by destabilization
0.788
In this report, we identified insulin receptor substrate 1 (IRS-1), a critical mediator of the insulin/insulin-like growth factor 1 signaling, as a proteolytic target of the CUL7 E3 ligase in a manner that depends on mammalian target of rapamycin and the p70 S6 kinase activities.Elimination of phosphorylation at S307/S312/S527/S636/S639 renders V5-IRS-1 partially resistant to degradation by Fbw8
SIGNOR-236599
Q9UPX8
O95886
0
relocalization
up-regulates activity
0.788
SHANK proteins are ‘master’ scaffolding proteins that tether and organize intermediate scaffolding proteins. They are located at excitatory synapses, where they are crucial for proper synaptic development and function. SAPAP proteins subsequently bind to the PDZ domain of members of the SHANK protein family. SHANK proteins then bind to the actin cytoskeleton and to Homer protein, which in turn interacts with mGluRs. Through these extended links, PSD95, SAPAP, SHANK and Homer proteins form a quaternary complex that brings together mGluR and NMDAR complexes in the PSD (FIG. 3).
SIGNOR-264593
O75197
P04628
0
binding
up-regulates activity
0.788
Ligands such as wnt1, wnt3a, and wnt8 couple the seventransmembrane domain receptor frizzled (fzd) and the single-membrane-spanning low-density receptor-related protein 5/6 (lrp5/6) to activate wnt?Beta-catenin signaling.
SIGNOR-169645
P48740
Q15485
0
binding
up-regulates activity
0.788
H-ficolin binds to PSA, a polysaccharide produced by Aerococcus viridans. C4 was activated by H-ficolin preparations bound to PSA which had been coated on ELISA plates. These results indicate that H-ficolin is a second ficolin which is associated with MASPs and sMAP, and which activates the lectin pathway|Proteolytic activation of complement components by H-ficolin-MASP.
SIGNOR-263411
Q05193
Q9Y5X1
0
binding
up-regulates
0.788
Snx9 binds directly to bothdynamin-1 anddynamin-2. Moreover by stimulatingdynaminassembly, snx9 stimulatesdynamin's basal gtpase activity and potentiates assembly-stimulated gtpase activity on liposomes.
SIGNOR-133892
Q15303
O14511
0
binding
up-regulates
0.788
The neuregulins (also called heregulins and neu differentiation factors) nrg-1 and nrg-2 bind erbb-3 and erbb-4;and nrg-3 and nrg-4 bind erbb-4.
SIGNOR-26211
P11142
O95817
0
binding
up-regulates activity
0.788
Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70.
SIGNOR-254116
Q13705
P08476
0
binding
up-regulates activity
0.787
Activin binds directly to ActR-IIB, and this complex associates with ActR-IB, which does not bind ligand on its own. In the resulting complex, ActR-IB becomes hyperphosphorylated, and this requires the kinase activity of ActR-IIB.
SIGNOR-235142
P46094
P47992
0
binding
up-regulates
0.787
Scm-1 showed a high-affinity binding to xcr1 with a kd of 10 nm and induced vigorous chemotaxis and calcium mobilization in xcr1-transfected murine l1.2 cells.
SIGNOR-71164
O43353
Q13489
0
polyubiquitination
up-regulates activity
0.787
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.
SIGNOR-272715
Q96PU5
O00141
0
phosphorylation
down-regulates activity
0.787
Site‐directed mutagenesis of the SGK1 phosphorylation sites in the Nedd4‐2 protein (S382A,S468ANedd4‐2) and in the EAAT1 protein (T482AEAAT1, T482DEAAT1) significantly blunts the effect of S422DSGK1. Introduction of a negative charge at the SGK phosphorylation site in the EAAT1 protein leads to a strong stimulation of the carrier, whereas replacement with alanine markedly decreases the EAAT1‐mediated current. These observations suggest that SGK1 exerts its effect not only by phosphorylation of Nedd4‐2 but also by phosphorylation of EAAT1.
SIGNOR-263076
P15924
Q99959
0
binding
up-regulates quantity by stabilization
0.787
In contrast to the proper membrane localization of PKP2 and DSP after cotransfection of both WT proteins, mutant PKP2 C796R protein was not able to interact with FLAG-DSP to enable assembly at the junctional plaque, indicating the requirement of functional PKP2 for DSP integration into the desmosome.
SIGNOR-261254
O75787
P00797
0
binding
up-regulates
0.787
We report the expression cloning of the human renin receptor complementary dna encoding a 350-amino acid protein with a single transmembrane domain and no homology with any known membrane protein. Transfected cells stably expressing the receptor showed renin- and prorenin-specific binding. The binding of renin induced a fourfold increase of the catalytic efficiency of angiotensinogen conversion to angiotensin i and induced an intracellular signal with phosphorylation of serine and tyrosine residues associated to an activation of map kinases erk1 and erk2
SIGNOR-88416
Q16665
P27540
0
binding
up-regulates activity
0.787
The functional transcription factor exists as a heterodimeric complex consisting of HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Association of HIF-1 with ARNT is required for its activity; however, no other role has been ascribed to this interaction.
SIGNOR-253720
P49682
P02778
0
binding
up-regulates activity
0.787
The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells.
SIGNOR-260969
P38398
O96017
0
phosphorylation
up-regulates
0.787
In this study, we tested the hypothesis that the brca1-mediated regulation of recombination requires the chk2- and atm-dependent phosphorylation sites.
SIGNOR-120575
Q92859
Q96B86
0
binding
down-regulates activity
0.787
Netrin-1-neogenin interactions mediate chemoattractive axon guidance, while RGMa-neogenin interactions repel axons. 
SIGNOR-268388
Q99835
Q13635
0
binding
down-regulates activity
0.786
We show that free Ptc (unbound by Hh) acts sub-stoichiometrically to suppress Smo activity and thus is critical in specifying the level of pathway activity.
SIGNOR-91709
P15692
P40763
0
transcriptional regulation
up-regulates quantity by expression
0.786
Stat3 directly regulated the promoter of the VEGF gene. Blockade of activated Stat3 by ectopic expression of dominant-negative Stat3 significantly inhibited VEGF expression, and the growth and metastasis of human pancreatic cancer cells. 
SIGNOR-259456
P23528
Q8WYL5
0
dephosphorylation
up-regulates activity
0.786
Differential activities, subcellular distribution and tissue expression patterns of three members of Slingshot family phosphatases that dephosphorylate cofilin.|Cofilin, a key regulator of actin filament dynamics, is inactivated by phosphorylation at Ser-3 by LIM-kinases and is reactivated by dephosphorylation by a family of protein phosphatases, termed Slingshot (SSH).
SIGNOR-248762
Q14457
Q9C0C7
0
binding
up-regulates activity
0.786
we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2.
SIGNOR-168252
P32238
P06307
0
binding
up-regulates
0.786
Cck8 interacts with nanomolar affinities with two different receptors designated cck-a and cck-b
SIGNOR-68474
P41597
P13500
0
binding
up-regulates activity
0.786
The investigators showed that myoblasts constitutively express receptors for CCL2 (CCR2), CCL3 (CCR1 and CCR5), and CCL4 (CCR5), and that stimulation with either CCL2 or CCL4 was sufficient to promote myoblast proliferation. 
SIGNOR-255113
P32248
O00585
0
binding
up-regulates
0.786
The regulated expression of the chemokine secondary lymphoid tissue chemokine (slc/ccl21) and its corresponding receptor, ccr7.
SIGNOR-117566
Q96RJ3
Q9Y275
0
binding
up-regulates activity
0.785
Baff specifically binds baff receptor
SIGNOR-135713
O14974
O75116
0
phosphorylation
down-regulates activity
0.785
Rho kinase is known to control smooth muscle contractility by phosphorylating the 110 kDa myosin-targetting subunit (MYPT1) of the myosin-associated form of protein phosphatase 1 (PP1M). Phosphorylation of MYPT1 at Thr695 has previously been reported to inhibit the catalytic activity of PP1. Here, we show that the phosphorylation of Thr850 by Rho kinase dissociates PP1M from myosin, providing a second mechanism by which myosin phosphatase activity is inhibited.
SIGNOR-249164
O60610
P61586
0
null
up-regulates activity
0.785
We find that the small GTPase Rho regulates R-cadherin adherens junction formation via Dia1 (also known as p140mDia) and profilin-1-mediated signaling pathway. The role played by Rho in regulating R-cadherin is underscored by the fact that constitutively active RhoA(Q63L) induces R-cadherin junction formation in MDA-MB-231 cells.|Data presented thus far demonstrated that Rho, Dia1, and profilin-1 were required for R-cadherin junction formation in N480 cells.
SIGNOR-253108
P30305
O14757
0
phosphorylation
down-regulates activity
0.785
Here, we show that cdc25b is phosphorylated by chk1 in vitro on multiple residues, including s230 and s563.We show that the s230-phosphorylated form of cdc25b is located at the centrosome from early s phase until mitosis. Furthermore, mutation of s230 to alanine increases the mitotic-inducing activity of cdc25b
SIGNOR-149898
O60934
Q13535
0
phosphorylation
up-regulates
0.785
We demonstrate that mrn and atr/atr-interacting protein (trip) interact with each other, and the forkhead-associated/breast cancer c-terminal domains (fha/brct) of nbs1 play a significant role in mediating this interaction. Mutations in the fha/brct domains do not prevent atr activation but specifically impair atr-mediated nbs1 phosphorylation at ser-343, which results in a defect in the s-phase checkpoint.
SIGNOR-155214
O15169
P48729
0
phosphorylation
up-regulates activity
0.785
Four sites, S80, S82, S222, and S473, were identified to be PP1 regulated (Supplementary Figure 3). Three of them (S80, S82, and S473) were also phosphorylated in vitro by CKI and are conserved between axin1 and axin2/conductin.|This suggests that cumulative phosphorylation of axin is required for it to fully downregulate Wnt/beta_catenin signaling.
SIGNOR-249191
P49238
P78423
0
binding
up-regulates
0.785
Fractalkine/cx3cl1 is a membrane-tethered chemokine that functions as a chemoattractant and adhesion protein by interacting with the receptor cx3cr1.
SIGNOR-109135
P62136
P41236
0
binding
down-regulates
0.785
Atm phosphorylates i-2 on serine 43, leading to the dissociation of the pp1-i-2 complex and the activation of pp1.
SIGNOR-160651
P24928
Q9NYV4
0
phosphorylation
up-regulates activity
0.784
Cyck/cdk12 can activate transcription and phosphorylate ser2 in the ctd of rnapii / phosphorylation of serine at position 2 (ser2) is thought to be responsible for productive transcriptional elongation and synthesis of full-length mature mrna
SIGNOR-176805
P04628
Q8N474
0
binding
down-regulates
0.784
Frp inhibits wnt signaling through interactions with wnt and/or formation of nonfunctional complexes with the frizzled receptor. here we demonstrate that frza, a sfrp that is highly expressed in vascular endothelium and a variety of epithelium, specifically binds to wnt-1 protein, but not wnt-5a protein, and modulates wnt-1 signaling.
SIGNOR-71423
P32248
Q99731
0
binding
up-regulates activity
0.784
CCL19 and CCL21 are endogenous agonists for the seven-trans membrane receptor CCR7.
SIGNOR-278123
P34925
P41221
0
binding
up-regulates
0.784
Purified human RYK binds to mouse Wnt1, 3a and 5a expressed in HEK293 cells. Separate experiments show that human RYK also immunopreciptitates human VANGL2 when the proteins are co-expressed in HEK293 cells.
SIGNOR-258970
P30550
P07492
0
binding
up-regulates
0.784
Indeed, many potent mitogens such as thrombin, lysophosphatidic acid (lpa), gastrin-releasing peptide (grp), endothelin and prostaglandins stimulate cell proliferation by acting on their cognate gpcrs in various cell types.
SIGNOR-152676
P24385
P49841
0
phosphorylation
down-regulates
0.783
Phosphorylation of cyclin d1 on a single threonine residue near the carboxyl terminus (thr-286) positively regulates proteasomal degradation of d1. Now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover now, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cyclin d1 specifically on thr-286, thereby triggering rapid cyclin d1 turnover.
SIGNOR-144818
Q9UKT4
P53350
0
phosphorylation
down-regulates
0.783
We propose that the balance of evi5 and polo-like kinase activities determines the timely accumulation of emi1 and cyclin, ensuring mitotic fidelity.
SIGNOR-142949
P32239
P01350
0
binding
up-regulates
0.783
A segment of five amino acids in the second extracellular loop of the cck-b receptor was shown to be essential for the high affinity of the natural peptide agonits, gastrin,
SIGNOR-66987
Q8WUP2
Q96AC1
0
binding
up-regulates activity
0.783
Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration.
SIGNOR-266108
P15391
P20023
0
binding
up-regulates activity
0.783
Complement receptor type 2 (CR2)/CD21 plays a key role in the development of high-affinity Abs and long-lasting memory to foreign Ags. When CR2 is bound by its primary C3 activation fragment–derived ligand, designated C3d, it coassociates with CD19 on B cells to amplify BCR signaling.
SIGNOR-266642
P12694
Q8N3J5
0
dephosphorylation
up-regulates activity
0.783
BCKD is inhibited by phosphorylation of its E1alpha subunit at Ser293, which is catalyzed by BCKD kinase. During BCAA excess, phosphorylated Ser293 (pSer293) becomes dephosphorylated through the concerted inhibition of BCKD kinase and the activity of an unknown intramitochondrial phosphatase. Using unbiased, proteomic approaches, we have found that a mitochondrial-targeted phosphatase, PP2Cm, specifically binds the BCKD complex and induces dephosphorylation of Ser293 in the presence of BCKD substrates
SIGNOR-248758
Q92843
O43521
0
binding
down-regulates
0.783
Bim binds prosurvival proteins comparably. The members that promote cell survival, including mammalian bcl-2, bcl-xl,bcl-w, mcl-1, and a1.
SIGNOR-133832
Q01718
P01189
0
binding
up-regulates activity
0.783
Here, we show that, whereas MRAP was essential for activation of MC2R signaling, MRAP2 was an endogenous inhibitor that competed with MRAP for binding to MC2R and decreased the potency of adrenocorticotropic hormone (ACTH), the endogenous agonist for MC2Rs, in stimulating the production of adenosine 3',5'-monophosphate (cAMP).
SIGNOR-268615
Q14203
P30622
0
binding
up-regulates activity
0.782
MT-unbound CLIP-170 can adopt a folded conformation through an intramolecular interaction of its terminal domains. Binding to MTs correlates with the unfolding of CLIP-170, which allows the interaction of the COOH-terminal domain with its binding partners, such as dynactin, resulting in their recruitment to the MT tip. The NH2 terminus of p150Glued binds directly to the COOH terminus of CLIP-170 through its second metal-binding motif.
SIGNOR-252164
P43694
Q8WW38
0
binding
down-regulates activity
0.782
FOG-2 associates physically with the N-terminal zinc finger of GATA-4 both in vitro and in vivo. This interaction appears to modulate specifically the transcriptional activity of GATA-4 because overexpression of FOG-2 in both NIH 3T3 cells and primary rat cardiomyocytes represses GATA-4-dependent transcription from multiple cardiac-restricted promoters.
SIGNOR-236959
Q96B36
P31749
0
phosphorylation
down-regulates activity
0.782
Treatment of these cells with 4-hydroxytamoxifen stimulated the phosphorylation of wt PRAS40 but not the mutant PRAS40 in which Thr-246 was mutated. These results demonstrate that activation of Akt alone is sufficient to induce phosphorylation of PRAS40
SIGNOR-252544
P46531
O14672
0
cleavage
up-regulates activity
0.782
ADAM10-mediated Notch1 cleavage is the rate limiting-step for release of the NICD and subsequent activation of Notch1 signaling. In T cells ADAM10-mediated Notch1 shedding controls T cell development
SIGNOR-259838
P01019
P12821
0
cleavage
up-regulates activity
0.782
Angiotensin I-converting enzyme is a zinc metallopeptidase that plays an important role in blood pressure regulation by cleaving the inactive decapeptide angiotensin I to angiotensin II, a potent vasopressor octapeptide.
SIGNOR-253326
P78552
P05112
0
binding
up-regulates
0.782
It is now known that this alternate receptor is a heterodimer, the type ii il-4 receptor or the il-13 receptor, which is comprised of IL-4R And IL-13R1.
SIGNOR-100759
P43220
P01275-PRO_0000011258
0
binding
up-regulates activity
0.782
GLP-1 and GIP exert their physiological actions via stimulation of the two G protein-coupled receptors (GPCRs): the GLP-1 receptor (GLP-1R) and the GIP receptor (GIPR), respectively.
SIGNOR-278133
P49682
Q07325
0
binding
up-regulates activity
0.782
The chemokines CXCL9, 10, and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T cells.
SIGNOR-260970
P56945
Q14289
0
phosphorylation
up-regulates activity
0.782
Pyk2 knockdown also decreased p130Cas.|p130Cas and paxillin can be phosphorylated by Fak or Pyk2, and bind directly to these kinases.
SIGNOR-280100
P43220
P01275
0
binding
up-regulates
0.782
In the present study we stably expressed the rat b-cell glp-i receptor in cho cells and studied binding characteristics and receptor activation utilizing the naturally occurring receptor agonist glp-i(7-36)-amide (glp-i), the proglucagon-derived glp-i-related peptide oxyntomodulin, the glp-i receptor agonist exendin-4, and the specific antagonist exendin
SIGNOR-34855
P04180
P02647
0
binding
up-regulates activity
0.782
Activation of LCAT by apolipoprotein (apo) A-I on nascent (discoidal) high density lipoproteins (HDL) is essential for formation of mature (spheroidal) HDL during the antiatherogenic process of reverse cholesterol transport. After attachment of LCAT to discoidal HDL, the helix 5/5 domains in apoA-I form amphipathic presentation tunnels for migration of hydrophobic acyl chains and amphipathic UC from the bilayer to the phospholipase A2-like and esterification active sites of LCAT, respectively.
SIGNOR-252103
Q9NT62
Q9BXW4
0
binding
up-regulates activity
0.782
Lc3-i is activated by the same atg7 involved in atg12 conjugation, transferred to atg3, a second e2-like enzyme, and finally conjugated to pe
SIGNOR-191552
P46531
Q86Y01
0
ubiquitination
up-regulates activity
0.781
The human Deltex (DTX1) gene encodes a cytoplasmic protein that functions as a positive regulator of the Notch signaling pathway.
SIGNOR-85942
P05412
P27361
0
phosphorylation
up-regulates
0.781
Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein.
SIGNOR-91379
P40238
P40225
0
binding
up-regulates
0.781
Thrombopoietin(tpo) controls the formation of megakaryocytes and platelets from hematopoietic stem cells via activation of the c-mplreceptorand multiple downstream signal transduction pathways.
SIGNOR-113955
P28482
Q16690
0
dephosphorylation
down-regulates
0.781
Here we demonstrate that dusp5, an inducible nuclear phosphatase, interacts specifically with erk2 via a kinase interaction motif (kim) within its amino-terminal noncatalytic domain. This binding determines the substrate specificity of dusp5 in vivo, as it inactivates erk2 but not jun n-terminal protein kinase or p38 map kinase.
SIGNOR-134049
P54132
O14757
0
phosphorylation
down-regulates quantity by destabilization
0.781
We now provide evidence that BLM undergoes K48-linked ubiquitylation and subsequent degradation during mitosis due to the E3 ligase, Fbw7α. Fbw7α carries out its function after GSK3β- and CDK2/cyclin A2-dependent phosphorylation events on Thr171 and Ser175 of BLM which lies within a well-defined phosphodegron, a sequence which is conserved in all primates.Phosphorylation on BLM Thr171 and Ser175 depends on prior phosphorylation at Thr182 by Chk1/Chk2. Thr182 phosphorylation not only controls BLM ubiquitylation and degradation during mitosis but is also a determinant for its localization on the ultrafine bridges.
SIGNOR-276909
P12931
P18031
0
dephosphorylation
up-regulates activity
0.781
Incubation of the inactivated c-Src with PTP1B results in a dose-dependent reactivation of c-Src tyrosine kinase activity. Incubation of c-Src with 2 or 10 g of PTP1B results in partial or full restoration of c-Src kinase activity, respectively. The activation is accompanied by dephosphorylation of c-Src, both of Tyr-419 and of Tyr-530
SIGNOR-245299
Q13158
Q15628
0
binding
up-regulates activity
0.781
Tradd recruits fadd
SIGNOR-177958
Q15796
Q96PU5
0
ubiquitination
down-regulates activity
0.781
Through its ww domain, nedd4l specifically recognizes a tgf-beta-induced phosphothr-protyr motif in the linker region, resulting in smad2/3 polyubiquitination and degradation
SIGNOR-217622
O14836
Q9Y275
0
binding
up-regulates
0.781
Tumor necrosis factor (tnf) receptor superfamily member taci is a high affinity receptor for tnf family members april and blys.
SIGNOR-81360