IdA
stringlengths 6
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| IdB
stringlengths 6
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| mechanism
stringclasses 40
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stringclasses 10
values | score
float64 0.1
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stringlengths 10
1.63k
⌀ | signor_id
stringlengths 12
14
|
|---|---|---|---|---|---|---|---|
Q86UP0
|
P35222
| 1
|
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
|
P51813
|
Q05397
| 1
|
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
|
P50613
|
P50750
| 1
|
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
|
P08603
|
P02741
| 1
|
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
|
P06241
|
P29350
| 1
|
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
|
Q99683
|
O95382
| 2
|
binding
|
up-regulates quantity by stabilization
| 0.551
|
C-terminal region of ASK1 binds to ASK2 and inhibits the degradation of ASK2
|
SIGNOR-260831
|
O15530
|
Q9BXL7
| 1
|
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
|
Q92963
|
P15056
| 1
|
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
|
Q96SL8
|
P54845
| 1
|
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
|
P35658
|
P84022
| 1
|
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
|
Q16539
|
Q14790
| 1
|
phosphorylation
|
down-regulates
| 0.55
|
P38-mapk can directly phosphorylate and inhibit the activities of caspase-8
|
SIGNOR-122103
|
P49407
|
Q9Y496
| 1
|
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
|
P00740
|
P08709
| 2
|
cleavage
|
up-regulates activity
| 0.55
|
The factor VII zymogen is cleaved at arginine 152 by a variety of proteases, including thrombin, factor IXa, factor Xa, and factor VIIa–tissue factor to produce the serine protease factor VIIa.
|
SIGNOR-263522
|
P00519
|
O00401
| 1
|
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
|
P41240
|
P16284
| 1
|
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
|
P15976
|
O15379
| 1
|
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
|
Q6W2J9
|
Q9UQL6
| 1
|
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
|
O00253
|
P33032
| 1
|
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
|
O96017
|
Q15717
| 1
|
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
|
P08709
|
P00740
| 2
|
binding
|
up-regulates activity
| 0.55
|
TF has a high affinity for FVII and enables the trace levels (∼1% of the total FVII) of activated FVII (FVIIa) in the blood to cleave specific sites in the serine proteases FIX and FX, activating them into FIXa and FXa, respectively.
|
SIGNOR-263544
|
Q9NWT6
|
P46531
| 1
|
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
|
P51617
|
P40763
| 1
|
phosphorylation
|
up-regulates
| 0.55
|
Irak1 can directly use stat3 as a substrate and cause stat3 serine 727 phosphorylation.
|
SIGNOR-129685
|
P12931
|
Q14118
| 1
|
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
|
O00631
|
O14983
| 1
|
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
|
P15735
|
P11217
| 1
|
phosphorylation
|
up-regulates activity
| 0.55
|
It is well-characterized that GP is activated by PhK-mediated serine phosphorylation at Ser-15
|
SIGNOR-267400
|
P04150
|
Q92831
| 1
|
relocalization
|
up-regulates activity
| 0.549
|
NR3C1 impaired GLI1 function by dynamically modulating the recruitment of PCAF acetyltransferase
|
SIGNOR-269233
|
Q96PE2
|
P61586
| 1
|
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
|
P29590
|
Q15796
| 1
|
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
|
Q9UQM7
|
Q15796
| 1
|
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
|
P06493
|
Q8TEM1
| 1
|
phosphorylation
|
up-regulates activity
| 0.549
|
In vitro phosphorylation of GST fusion protein containing the carboxyl-terminal domain of gp210 by cyclin B-p34cdc2 protein kinase generates a phosphopeptide that comigrates with a mitosis-specific phosphopeptide. Ser1880 Is the Mitotic Phosphorylation Site of Gp210.
|
SIGNOR-262699
|
Q13418
|
Q96A00
| 1
|
phosphorylation
|
up-regulates activity
| 0.549
|
Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ilk predominantly phosphorylated the site critical for potent inhibition, i.e. Thr(38) of cpi-17
|
SIGNOR-90828
|
Q9NRX4
|
O15554
| 1
|
dephosphorylation
|
down-regulates activity
| 0.549
|
We now show that the mammalian protein histidine phosphatase (PHPT-1) directly binds and inhibits KCa3.1 by dephosphorylating histidine 358 on KCa3.1.|Overexpression of wild-type, but not a phosphatase dead, PHPT-1 inhibited KCa3.1 channel activity.
|
SIGNOR-277071
|
P04626
|
Q92529
| 1
|
relocalization
|
up-regulates
| 0.549
|
Erbb3 is characterized by a large number of binding sites for phosphatidylinositol-3-kinase (pi3k), while erbb2 has only few interaction partners with shc as the most frequent one.
|
SIGNOR-146855
|
Q13315
|
Q9NS23
| 1
|
phosphorylation
|
up-regulates
| 0.549
|
We show that, upon dna damage, rassf1a is phosphorylated by atm on ser131 and is involved in the activation of both mst2 and lats1, leading to the stabilization of p73.
|
SIGNOR-161934
|
O14980
|
P04637
| 1
|
relocalization
|
down-regulates activity
| 0.549
|
We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus.
|
SIGNOR-260067
|
P54257
|
Q8N157
| 1
|
binding
|
up-regulates activity
| 0.549
|
Huntingtin-associated protein-1 (Hap1) is a regulatory protein that binds Ahi1, and Hap1 knock-out mice have been reported to have JBTS-like phenotypes, suggesting a role for Hap1 in ciliogenesis.
|
SIGNOR-269081
|
O60282
|
O60296
| 1
|
binding
|
up-regulates activity
| 0.549
|
Trafficking kinesin proteins (TRAKs) are kinesin adaptors. They bind the cargo binding domain of kinesin-1 motor proteins forming a link between the motor and their cargoes. This supports the idea that the KIF5A–TRAK2 interaction is multivalent and could act to ensure stable motor-cargo interaction during intracellular trafficking; dimerization of both motor and adaptor molecules further enhances this stability (Fig. 6). A similar multivalent profile was found for the TRAK2 binding site within the kinesin-1 isoform, KIF5C.
|
SIGNOR-264064
|
O95644
|
P05112
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.549
|
Recombinant NFAT1 can mediate transcription of the interleukin-2, interleukin-4, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor promoters in T cells, suggesting that NFAT1 contributes to the CsA-sensitive transcription of these genes during the immune response.
|
SIGNOR-254498
|
P49841
|
Q68CJ9
| 1
|
phosphorylation
|
down-regulates activity
| 0.549
|
It is possible that phosphorylation of CREBH by GSK3beta leads to altered CREBH conformation with a resulting decreased affinity toward the COPII coated transport complex.|Similarly, expression of dominant negative GSK3beta can rescue the decreased CREBH cleavage activity in the Bmal1 knockdown hepatocytes under the circadian clock (XREF_FIG), thus confirming that BMAL1 controls circadian regulated CREBH cleavage and activation through AKT and GSK3beta signaling in hepatocytes.
|
SIGNOR-279785
|
P10589
|
P19793
| 1
|
binding
|
up-regulates
| 0.549
|
Arp-1/rxr, coup-tfi/rxr, and arp-1/coup-tfi heterodimers bound the fp330-3' site
|
SIGNOR-79440
|
Q9UK99
|
Q9UKC9
| 1
|
binding
|
down-regulates quantity by destabilization
| 0.549
|
F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Here we show that another F-box protein Fbxo3, belonging to the FBXO type protein family, also interacts with and targets Smurf1 for poly-ubiquitination and proteasomal degradation. The SCF complex is composed of F-box protein, Skp1, Cullin1 (Cul1) and ROC1. Fbxo3, whose substrates are few, forms SCF Fbxo3 ubiquitin ligase and regulates the degradations of Fbxl2, p62, HIPK2 and p300 through the ubiquitin-proteasome pathway.
|
SIGNOR-272445
|
Q9H2K2
|
P54274
| 1
|
ADP-ribosylation
|
down-regulates activity
| 0.549
|
Tankyrase 2 poly(ADP-ribosyl)ated itself and TRF1. Overexpression of tankyrase 2 in the nucleus released endogenous TRF1 from telomeres.
|
SIGNOR-263376
|
Q6P4F7
|
P61586
| 1
|
gtpase-activating protein
|
down-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-260466
|
Q9Y4K3
|
O75385
| 1
|
ubiquitination
|
up-regulates quantity by stabilization
| 0.548
|
AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function.
|
SIGNOR-273000
|
P35462
|
P63096
| 1
|
binding
|
up-regulates activity
| 0.548
|
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-256702
|
O14920
|
Q9NQC7
| 1
|
phosphorylation
|
down-regulates activity
| 0.548
|
Thus, serine 418 is phosphorylated in vivo.Cyld phosphorylation may serve as a mechanism to inactivate its traf2 deubiquitination activity.
|
SIGNOR-204716
|
P48380
|
Q92949
| 1
|
binding
|
up-regulates activity
| 0.548
|
RFX3 acts as a transcriptional co-activator to FOXJ1 that enhances the expression of cilia-associated genes. FOXJ1 is an important regulator of cilia gene expression during ciliated cell differentiation, with RFX3 as a transcriptional co-activator to FOXJ1, helping to induce the expression of cilia genes in the process of ciliated cell differentiation of basal/progenitor cells.
|
SIGNOR-266929
|
Q9P227
|
P61586
| 1
|
gtpase-activating protein
|
down-regulates activity
| 0.548
|
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-260479
|
Q15119
|
P29803
| 1
|
phosphorylation
|
down-regulates
| 0.548
|
Kinetic and regulatory properties of recombinant human pdh2 and pdh1 were compared in this study. Site-specific phosphorylation/dephosphorylation of the three phosphorylation sites by four pdh kinases (pdk1-4) and two pdh phosphatases (pdp1-2) were investigated by substituting serines with alanine or glutamate in pdhs.
|
SIGNOR-143970
|
P36897
|
P29353
| 1
|
phosphorylation
|
up-regulates
| 0.548
|
We now report that upon TGF-_ stimulation, T_RI phosphorylates ShcA on serine and, to a lesser degree, on tyrosine to activate Erk MAP kinases.
|
SIGNOR-227503
|
O43933
|
P50542
| 1
|
binding
|
up-regulates activity
| 0.548
|
Pex1, Pex6, and Pex26 are involved in Pex5 export from peroxisomes., we found that Pex1 and Pex6 bind to Pex5 (Fig. (Fig.6). Therefore, it is conceivable that Pex1 and Pex6 pull out Pex5 from peroxisome membranes in an ATP-dependent manner.
|
SIGNOR-253618
|
P38398
|
Q13085
| 1
|
binding
|
down-regulates activity
| 0.548
|
ACCA binds BRCA1 when phosphorylated onSer1263, thus supporting a model in which controlof lipid synthesis would be mediated at least in part,viaphosphorylation of the Ser1263.
|
SIGNOR-267474
|
O14672
|
P12830
| 1
|
cleavage
|
up-regulates activity
| 0.548
|
The ADAM proteases are best known for their role in shedding the extracellular domain of transmembrane proteins. Among the transmembrane proteins shed by ADAM10 are notch, HER2, E-cadherin, CD44, L1 and the EGFR ligands, EGF and betacellulin.
|
SIGNOR-259846
|
P58417
|
Q9ULB1
| 1
|
binding
|
up-regulates
| 0.548
|
Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1
|
SIGNOR-62775
|
P15927
|
O60934
| 1
|
binding
|
up-regulates
| 0.548
|
The response to replication stress requires the recruitment of rpa and the mre11-rad50-nbs1 (mrn) complex. We observe a direct interaction between rpa with both nbs1 and mre11. By utilizing rpa bound to ssdna, we demonstrate that substituting rpa with phosphorylated rpa or a phosphomimetic weakens the interaction with the mrn complex.
|
SIGNOR-186651
|
P58417
|
P58400
| 1
|
binding
|
up-regulates
| 0.548
|
Purification of neurexin ialpha revealed that it is tightly complexed to a secreted glycoprotein called neurexophilin 1
|
SIGNOR-62699
|
P34947
|
O75581
| 1
|
phosphorylation
|
up-regulates
| 0.548
|
we found that g protein-coupled receptor kinases 5 and 6 (grk5/6), traditionally known to phosphorylate and desensitize 7tm g protein-coupled receptors, directly phosphorylate the pppsp motifs on single transmembrane lrp6 and regulate wnt/lrp6 signaling
|
SIGNOR-23330
|
Q9Y261
|
P32243
| 1
|
binding
|
down-regulates activity
| 0.548
|
Here we show that OTX2 directly associates with LIM1 and HNF-3beta. The luciferase assay with the P3C sequence, a specific DNA binding sequence for paired-class homeobox genes, has demonstrated that LIM1 enhances, but HNF-3beta represses, OTX2-directed gene expression.
|
SIGNOR-221164
|
P42658
|
Q9NZV8
| 1
|
relocalization
|
up-regulates activity
| 0.548
|
DPPX-S reduced energy barriers of the voltage-dependent transitions; therefore, this auxiliary subunit may exert a catalytic effect on voltage-dependent gating of Kv4.2 channels. DPPX-S may also accelerate coupled inactivation indirectly
|
SIGNOR-269005
|
Q92915
|
Q9UQD0
| 1
|
binding
|
down-regulates activity
| 0.547
|
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-253413
|
P24941
|
Q15910
| 1
|
phosphorylation
|
up-regulates activity
| 0.547
|
Here, we demonstrate that the phosphorylation of EZH2 by cyclin-dependent kinases at Thr416 creates a docking site for the ForkHead-associated domain of NIPP1.
|
SIGNOR-255656
|
P42224
|
P14316
| 1
|
binding
|
up-regulates activity
| 0.547
|
We show that IRF-2 forms a complex with STAT1 and the cytokine-responsive region of the TAP1 promoter in any TPO or IFN-gamma target cells tested. Interaction of IRF-2 and STAT1 on the promoter depends on the DNA-binding domain of IRF-2.
|
SIGNOR-254532
|
P08238
|
P29474
| 1
|
binding
|
up-regulates activity
| 0.547
|
Here we show that Hsp90 associates with endothelial nitric oxide synthase (eNOS) and is rapidly recruited to the eNOS complex by agonists that stimulate production of nitric oxide, namely vascular endothelial growth factor, histamine and fluid shear stress. Moreover, the binding of Hsp90 to eNOS enhances the activation of eNOS.
|
SIGNOR-252214
|
Q13547
|
P15172
| 1
|
binding
|
down-regulates
| 0.547
|
Interaction of myod with hdac1 in undifferentiated myoblasts mediates repression of muscle-specific gene expression.
|
SIGNOR-111243
|
P10275
|
P04150
| 2
|
binding
|
down-regulates quantity by repression
| 0.547
|
Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity
|
SIGNOR-48513
|
P41968
|
Q5JWF2
| 1
| null |
up-regulates activity
| 0.547
|
We hypothesize that XLαs may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus.
|
SIGNOR-253068
|
Q8TF40
|
P07900
| 1
|
binding
|
down-regulates activity
| 0.547
|
FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.
|
SIGNOR-261413
|
P04629
|
O14492
| 1
|
phosphorylation
|
up-regulates
| 0.547
|
Two substrates of trk kinases, raps and sh2-b. raps and sh2-b mediate trk signaling in developing neurons
|
SIGNOR-62619
|
P54829
|
Q13224
| 1
|
dephosphorylation
|
down-regulates activity
| 0.547
|
These previous results, together with the present findings, indicate that STEP61 dephosphorylates the NR2B subunit at its regulatory tyr1472 site, and dephosphorylation of this site leads to internalization of the NMDAR complex from neuronal surface membranes.
|
SIGNOR-265744
|
P29590
|
P84022
| 1
|
binding
|
up-regulates activity
| 0.547
|
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-232090
|
P21246
|
Q9UM73
| 1
|
binding
|
up-regulates
| 0.547
|
We conclude from this series of experiments that ptn specifically binds to the alk orphan receptor as a high affinity ligand at least in part via the putative ligand binding domain described above.
|
SIGNOR-106411
|
O60285
|
P04637
| 1
|
phosphorylation
|
up-regulates
| 0.547
|
Here we showed that in the presence of wild-type lkb1, nuak1 directly interacts with and phosphorylates p53 in vitro and in vivo.
|
SIGNOR-172008
|
Q02156
|
O14920
| 1
|
phosphorylation
|
up-regulates activity
| 0.547
|
Monoubiquitylated PKC\u03b5 interacts with a ubiquitin-binding domain in NEMO zinc finger and recruits the cytosolic IKK complex to the plasma membrane, where PKC\u03b5 phosphorylates IKK\u03b2 at Ser177 and activates IKK\u03b2.|These results indicate that PKCepsilon phosphorylates IKKbeta at S177 and activates IKKbeta, which in turn induces PKM2 upregulation.
|
SIGNOR-278323
|
P17252
|
P15311
| 1
|
phosphorylation
|
up-regulates
| 0.547
|
Phosphorylation of ezrin is required for both conformational activation and for signaling to downstream events. The activating c-terminal threonine phosphorylation on t567 was first described to be downstream of the rho pathway (matsui et al., 1998). Additional studies have implicated protein kinase c (pkc) in the phosphorylation of ezrin t567.
|
SIGNOR-133223
|
P12931
|
P07355
| 1
|
phosphorylation
|
up-regulates
| 0.547
|
Translocation requires the presence of the annexin 2 binding partner p11 (s100a10) and the phosphorylation of annexin 2 at tyr23 through a src-like tyrosine kinase-dependent mechanism both in vitro and in vivo.
|
SIGNOR-127872
|
P56279
|
P31751
| 1
|
binding
|
up-regulates
| 0.547
|
Full-length tcl1 and its isoforms bind to akt / in in vitro kinase assays using gsk-3_ as a substrate, we found that the presence of any of the tcl1 family proteins (tcl1, mtcp1, or tcl1b) as gst fusion proteins significantly enhanced akt-induced gsk-3_ phosphorylation
|
SIGNOR-81683
|
P04150
|
P10275
| 2
|
binding
|
down-regulates activity
| 0.547
|
Androgen and glucocorticoid receptor heterodimer formation. A possible mechanism for mutual inhibition of transcriptional activity.
|
SIGNOR-48516
|
P41968
|
P63092
| 1
|
binding
|
up-regulates activity
| 0.547
|
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-268702
|
O43293
|
O14974
| 1
|
phosphorylation
|
down-regulates activity
| 0.547
|
We conclude from our results Par-4 operates through a "padlock" model in which binding of Par-4 to MYPT1 activates MP by blocking access to the inhibitory phosphorylation sites, and inhibitory phosphorylation of MYPT1 by ZIPK requires "unlocking" of Par-4 by phosphorylation and displacement of Par-4 from the MP complex.|We have also demonstrated that Par-4 is required for agonist induced, ZIPK mediated inhibition of MYPT1 and thus is an important amplifier of inputs to MP.
|
SIGNOR-279030
|
Q16654
|
P29803
| 1
|
phosphorylation
|
down-regulates
| 0.547
|
Pyruvate dehydrogenase (pdh) activity (pdha) controls the entry of carbohydrate into the tricarboxylic cycle and is regulated by pdh kinase (pdk), which phosphorylates and inactivates the enzyme, and pdh phosphatase, which dephosphorylates the enzyme to the active form
|
SIGNOR-121936
|
Q09472
|
P35558
| 1
|
acetylation
|
down-regulates quantity by destabilization
| 0.546
|
Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase|P300 Acetylates and Destabilizes PEPCK1|Furthermore, coexpression of P300 increased acetylation levels of wild-type PEPCK1, but not PEPCK13K/R, indicating that P300 acts on these lysine residues of PEPCK1
|
SIGNOR-267603
|
Q15418
|
Q8N122
| 1
|
phosphorylation
|
up-regulates
| 0.546
|
Ser719, ser721, and ser722 are the predominant rsk-dependent phosphorylation sites in raptor raptor phosphorylation regulates mtorc1 activity
|
SIGNOR-180466
|
Q96GD4
|
P17661
| 1
|
phosphorylation
|
down-regulates
| 0.546
|
We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. In the present study, we found aurora-b phosphorylates desmin at ser-11, thr-16, and ser-59, in vitro.
|
SIGNOR-100107
|
Q05513
|
Q9Y243
| 1
|
phosphorylation
|
up-regulates activity
| 0.546
|
Full activation of the PKB enzyme requires phosphorylation of a threonine in the activation
|
SIGNOR-249153
|
Q05209
|
P56945
| 1
|
dephosphorylation
|
down-regulates
| 0.546
|
Ptp-pest is an efficient negative regulator of lymphocyte activation. This function correlated with the ability of ptp-pest to induce dephosphorylation of shc, pyk2, fak and cas, and inactivate the ras pathway.
|
SIGNOR-109032
|
P49137
|
P09917
| 1
|
phosphorylation
|
up-regulates activity
| 0.546
|
Arachidonic acid promotes phosphorylation of 5-lipoxygenase at Ser-271 by MAPK-activated protein kinase 2 (MK2). when stimulated with only exogenous arachidonic acid, activity for the S271A mutant was significantly lower as compared with wild type 5-LO.
|
SIGNOR-250143
|
P50613
|
P10276
| 1
|
phosphorylation
|
up-regulates
| 0.546
|
However, only the coexpression of cdk7 stimulated ser-77 phosphorylation in vivo and enhanced transactivation by rar alpha, but not by a s77a rar mutant.
|
SIGNOR-49693
|
Q13418
|
Q8TAE6
| 1
|
phosphorylation
|
up-regulates activity
| 0.546
|
Pka predominantly phosphorylated a site distinct from the inhibitory t73 in kepi. Integrin-linked kinase phosphorylated KEPI (T73) and this dramatically increased inhibition of PP1c
|
SIGNOR-101835
|
Q96T91
|
P16473
| 1
|
binding
|
up-regulates
| 0.546
|
Recombinant a2/b5 heterodimeric glycoproteins, purified using cation exchange and size fractionation chromatography, activated human tsh receptors, but not lh and fsh receptors, and showed high affinity to tsh receptors in a radioligand receptor assay
|
SIGNOR-88614
|
O75925
|
P17844
| 1
|
sumoylation
|
up-regulates
| 0.546
|
We demonstrate that the sumo e3 ligase pias1 interacts with p68 and enhances its sumo modification in vivo / sumo modification enhances p68 transcriptional repression activity and inhibits the ability of p68 to function as a coactivator of p53.
|
SIGNOR-153719
|
Q9Y3S1
|
Q9H4A3
| 1
|
phosphorylation
|
up-regulates activity
| 0.546
|
WNK1, which is activated in response to osmotic stress by phosphorylation of its T-loop residue (Ser382). | We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.
|
SIGNOR-260790
|
P06702
|
O00206
| 1
|
binding
|
up-regulates activity
| 0.546
|
RAGE and TLR4 are well-characterized S100A8 and S100A9 receptors and expressed in AML cells. S100A9 binds to TLR4 and induces signaling pathways,promoting leukemic cell differentiation and proliferation arrest. Binding of S100A9 to TLR4 stimulates the phosphorylation of JNK, ERK1/2, and p38 MAPK, which leads to the activation of c-Jun, CREB, and NF-kB.
|
SIGNOR-261918
|
Q96FW1
|
P03372
| 1
|
deubiquitination
|
down-regulates activity
| 0.546
|
OTU Domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) deubiquitinates estrogen receptor (ER) alpha and affects ERalpha transcriptional activity.|We show that OTUB1 negatively regulates transcription mediated by ERalpha in transient reporter gene assays and transcription mediated by endogenous ERalpha in Ishikawa endometrial cancer cells.
|
SIGNOR-276529
|
Q8IWW6
|
P63000
| 1
|
gtpase-activating protein
|
down-regulates activity
| 0.546
|
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-260469
|
Q15831
|
O60285
| 1
|
phosphorylation
|
up-regulates
| 0.546
|
A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold.
|
SIGNOR-122686
|
Q9UM73
|
P19174
| 1
|
binding
|
up-regulates
| 0.546
|
Proteins that interact with alk tyrosine kinase play important roles in mediating downstream cellular signals. Previously reported proteins in the alk signal pathway were identified including pi3-k, jak2, jak3, stat3, grb2, irs, and plcgamma1.
|
SIGNOR-122082
|
Q9HCP0
|
O75581
| 1
|
phosphorylation
|
up-regulates
| 0.545
|
Ck1gamma is associated with lrp6, which has multiple, modular ck1 phosphorylation sites. Wnt treatment induces the rapid ck1gamma-mediated phosphorylation of these sites within lrp6
|
SIGNOR-143029
|
Q06124
|
P43405
| 1
|
dephosphorylation
|
down-regulates activity
| 0.545
|
Another SHP isoform, SHP-2, has been linked to negative regulation of Syk.|Syk and LAT are differentially dephosphorylated by SHP-2 and SHP-1, respectively.
|
SIGNOR-277085
|
Q9UNH5
|
P30291
| 1
|
dephosphorylation
|
up-regulates quantity by stabilization
| 0.545
|
In particular, we found that Cdc14A inhibits Wee1 degradation through the dephosphorylation of Ser-123 and Ser-139 residues.
|
SIGNOR-267470
|
P03372
|
O00459
| 1
|
binding
|
up-regulates
| 0.545
|
Recently, it has been known that er activates phosphatidylinositol-3-oh kinase (pi3k) through binding with the p85 regulatory subunit of pi3k.
|
SIGNOR-140473
|
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