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14
P41240
P46531
2
binding
up-regulates
0.281
We found that the notch-1-furin interaction is regulated by the non-receptor tyrosine kinase, c-src. c-src and notch-1 are physically associated, and this association is responsible for notch-1 processing and activation
SIGNOR-196824
Q8NFU7
P60484
1
transcriptional regulation
up-regulates quantity by expression
0.373
We also found that TET1 directly binds to the promoter region of PTEN and activates its transcription through demethylation of CpG islands
SIGNOR-259096
P22607
P22607
2
phosphorylation
up-regulates activity
0.2
Ligand stimulation leads to autophosphorylation of fgfr3 the absence of y577 (3y-577f) or y760 (3y-760f) resulted in a modest decrease in activity.
SIGNOR-106726
O95153
Q86UR5
2
binding
down-regulates activity
0.2
SH3 domains of RBPs interact with RIMs. The enhancement of depolarization-induced secretion in PC12 cells by fusion proteins that suppress the associations of RBPs with RIMs and α1 suggests that RBPs may repress RIMs, either directly or through associated proteins.
SIGNOR-264363
P08670
Q05513
0
phosphorylation
up-regulates activity
0.2
Results suggest that aPKCs target multiple activation sites (Ser33/39/56) on Vimentin and therefore is essential for VIF dynamics regulation during the metastasis of prostate cancer cells.
SIGNOR-277622
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
P10827
P19793
2
binding
up-regulates
0.663
Like many receptors belonging to the superfamily of steroid/thyroid nuclear receptors, thyroid hormone receptors (trs) bind to specific th-dna responsive elements (tre) upstream of target gene in heterodimeric complex with the 9-cis retinoid acid receptor (rxr).
SIGNOR-81446
P27361
P41212
1
phosphorylation
down-regulates
0.317
Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation.
SIGNOR-123656
Q00613
Q9H422
0
phosphorylation
up-regulates activity
0.335
We show that Yak1 directly phosphorylates Hsf1 in vitro, leading to the increase in DNA binding activity of Hsf1.
SIGNOR-279054
Q8TDY2
Q8IYT8
0
phosphorylation
up-regulates activity
0.747
When mTOR is inhibited, ULK1 and ULK2 activate and phosphorylate ATG13 and FIP200.
SIGNOR-280159
P35222
Q13616
0
ubiquitination
down-regulates quantity by destabilization
0.598
These results indicate that the cul1/skp1/beta-trcp complex forms a ubiquitin ligase that mediates the degradation of beta-catenin.
SIGNOR-64499
P62380
O96017
0
phosphorylation
down-regulates activity
0.291
In vitro, TRF2 was phosphorylated by recombinant Chk2 ( Figure\u00a04 C) on residues located in the first 350 aa ( Figure\u00a0S11 ).|To evaluate whether Chk2 activity affected the binding of TRF2 for telomeric TTAGGG repeats in duplex DNA, electrophoretic mobility shift assays (EMSA) were performed in the presence of ATP to allow phosphorylation and found that in contrast to Chk2 KD, Chk2 WT decreased the binding of TRF2 to DNA.
SIGNOR-280227
Q9BVJ7
Q9NP62
1
dephosphorylation
up-regulates quantity by stabilization
0.464
DUSP23 prevents GCM1 from ubiquitination and prolongs the half-life of GCM1.|Second, DUSP23 is able to dephosphorylate Ser322 in GCM1 in vitro and in a stable cell line expressing HA-GCM1.
SIGNOR-276982
Q15139
P17252
0
phosphorylation
up-regulates
0.441
These results provide direct evidence that pkd becomes activated in vivo as a consequence of pkc-mediated phosphorylation of serines 744 and 748.
SIGNOR-66666
O60260
Q9Y2N7
1
ubiquitination
down-regulates quantity by destabilization
0.2
Here we show that IPAS is a key molecule involved in neuronal cell death in Parkinson's disease (PD). IPAS was ubiquitinated by Parkin for proteasomal degradation following carbonyl cyanide m-chlorophenyl hydrazone treatment. Phosphorylation of IPAS at Thr12 by PTEN-induced putative kinase 1 (PINK1) was required for ubiquitination to occur.
SIGNOR-263089
P42768
P07948
0
phosphorylation
up-regulates activity
0.378
We demonstrated that WASP is phosphorylated on tyrosine 291 in macrophages, and the WASP phosphorylation is important for the phagocytic cup formation. In addition, we showed that WASP and WASP-interacting protein (WIP) form a complex at the phagocytic cup and that the WASP.WIP complex plays a critical role in the phagocytic cup formation. 
SIGNOR-273959
P61586
Q8WZ19
2
binding
down-regulates quantity
0.377
BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.
SIGNOR-264236
Q13418
P23528
1
phosphorylation
down-regulates
0.35
Actin (de)polymerization is regulated by cofilin, the ser(3) phosphorylation (ps(3)cofilin) of which inhibits its actin-severing activity. To determine how ilk regulates ps(3)cofilin, we examined the effects of ilk on ps(3)cofilin using normal rie1 cells.
SIGNOR-160756
P60763
Q99828
2
binding
up-regulates activity
0.348
We here report that CIB, a protein that binds to the alpha(IIb)beta(3) fibrinogen receptor, interacts exclusively with activated (V12) Rac3 but not Rac1 or Rac2. Binding of V12Rac3 to CIB was mediated by the C-terminal end of Rac3 and by Rac3 membrane localization
SIGNOR-269060
P43403
P06239
0
phosphorylation
up-regulates activity
0.619
We show that ZAP-70 has a primary autophosphorylation site at Tyr-292, with a secondary site at Tyr-126. We also show additional phosphorylation at Tyr-69, Tyr-178, Tyr-492, and Tyr-493 upon the addition of the protein tyrosine kinase, p56lck
SIGNOR-249375
Q9NRD5
Q6ZN44
2
binding
up-regulates activity
0.288
Recently, our laboratory showed that UNC5A is coimmunoprecipitated with PICK1 and PKCα. Moreover, we demonstrated that the association of PKCα with UNC5A depends on the activation of PKCα and the ability of UNC5A to bind PICK1
SIGNOR-268181
O95407
O95150
2
binding
down-regulates
0.709
Tl1a, is a ligand for dr3 and decoy receptor tr6/dcr3. Tr6-fc protein antagonizes nf-kappab activation and apoptosis induced by tl1a
SIGNOR-116256
P22612
P46019
1
phosphorylation
down-regulates activity
0.325
Phosphorylation of the alpha and beta subunits by the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) also relieves inhibition of the gamma subunit and thereby activates the enzyme.
SIGNOR-267414
Q08J23
Q96GD4
0
phosphorylation
down-regulates
0.72
Aurora-b phosphorylated nsun2 at ser139. Aurora-b-phosphorylation and the phosphorylation-mimic mutation (s139e) suppressed methyltransferase activities of nsun2.
SIGNOR-152001
P78527
Q13315
2
phosphorylation
down-regulates activity
0.702
It has also been reported that DNA-PKcs could inhibit ATM activity by directly phosphorylating ATM at T86 / T373 and T1985 / S1987 / S1988 sites .|It has also been reported that DNA-PKcs could inhibit ATM activity by directly phosphorylating ATM at T86 and T373 and T1985/S1987/S1988 sites.
SIGNOR-278324
P62140
P29474
1
dephosphorylation
up-regulates activity
0.2
The increase in eNOS activity coincided with specific dephosphorylation of eNOS-Thr495, known to enhance eNOS activity. Inhibition of protein phosphatase 1 (PP1) by calyculin A, tautomycetin, or siRNA against PP1 reversed NF-induced eNOS-Thr495 dephosphorylation
SIGNOR-248574
P49674
O60716
1
phosphorylation
down-regulates
0.288
Moreover, in response to wnt3a, p120-catenin is phosphorylated at ser268, a modification dependent on ck1epsilon activity, which disrupts its interaction with e-cadherin and, subsequently, with lrp5/6, promoting the release of ck1epsilon/p120-catenin from the wnt receptor complex.
SIGNOR-24443
P14136
Q96GD4
0
phosphorylation
down-regulates activity
0.438
We report here that aurora-b phosphorylates gfap and desmin in vitro, and this phosphorylation leads to a reduction in filament forming ability. The sites phosphorylated by aurora-b;thr-7/ser-13/ser-38 of gfap, and thr-16 of desmin are common with those related to rho-associated kinase (rho-kinase), which has been reported to phosphorylate gfap and desmin at cleavage furrow during cytokinesis. We identified ser-59 of desmin to be a specific site phosphorylated by aurora-b in vitro.
SIGNOR-100173
Q9NYU1
O60613
2
binding
up-regulates activity
0.2
The enzymatic activity of UGGT2 is enhanced by complex formation with Sep15
SIGNOR-261373
Q8NBP7
Q12772
0
transcriptional regulation
up-regulates quantity by expression
0.465
Recent studies have demonstrated that PCSK9 mRNA expression was upregulated to a greater extent than that of the LDL receptor in human hepatocytes in primary culture. Our findings also support the role of SREBP-2 as a transcriptional regulator of both the LDL receptor and PCSK9 in human enterocytes.
SIGNOR-254459
P22681
P46108
2
binding
up-regulates
0.824
These results indicate that crk binds to c-cbl in a tyrosine phosphorylation-dependent manner.
SIGNOR-39241
Q5JTC6
O75581
2
binding
up-regulates activity
0.478
Knockdown of Amer1 reduces Wnt-induced LRP6 phosphorylation, Axin translocation to the plasma membrane and formation of LRP6 signalosomesThe generation of PtdIns(4,5)P2 in regions of receptor activity triggers the recruitment of Amer1 proteins, which in turn promote LRP6 phosphorylation by recruiting Axin/GSK3_ and CK1gamma to LRP6.
SIGNOR-24265
P54646
Q15831
0
phosphorylation
up-regulates
0.627
We demonstrated that lkb1 phosphorylates ampk on the activation loop threonine (thr172) within the catalytic subunit and activates ampk in vitro. Here, we have investigated whether lkb1 corresponds to the major ampkk activity present in cell extracts. Ampkk purified from rat liver corresponds to lkb1, and blocking lkb1 activity in cells abolishes ampk activation in response to different stimuli
SIGNOR-122725
O14904
P02708
2
binding
up-regulates
0.2
We identified five wnts (wnt9a, wnt9b, wnt10b, wnt11, and wnt16) that are able to stimulate achr clustering, of which wnt9a and wnt11 are expressed abundantly in developing muscles.
SIGNOR-195972
P17706
P42224
1
dephosphorylation
down-regulates activity
0.734
Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.
SIGNOR-133279
P43405
O14757
0
phosphorylation
down-regulates
0.311
We found that chk1 phosphorylated the tumor suppressor spleen tyrosine kinase (l) (syk[l]) and identified the phosphorylation site at ser295. Furthermore, chk1 phosphorylation of syk(l) promoted its subsequent proteasomal degradation.
SIGNOR-197528
P08631
P63092
2
binding
up-regulates activity
0.2
Galphas and Galphai similarly modulate Hck, another member of Src-family tyrosine kinases.
SIGNOR-256529
O00763
P54646
0
phosphorylation
down-regulates activity
0.649
The results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK.
SIGNOR-250318
P28360
P50458
2
binding
down-regulates activity
0.477
Protein complex formation between Msx1 and Lhx2 homeoproteins is incompatible with DNA binding activity
SIGNOR-241330
Q9UBD9
P26992
2
binding
up-regulates
0.702
Striking phenotypic differences between cntf- and cntfr-deficient mice suggest that cntfr serves as a receptor for a second, developmentally important ligand. We have identified this factor as a stable secreted complex of cardiotrophin-like cytokine (clc) and the soluble receptor cytokine-like factor-1 (clf).
SIGNOR-81376
Q96GD4
Q12888
1
phosphorylation
up-regulates activity
0.409
Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.
SIGNOR-264411
P48729
O15151
1
phosphorylation
up-regulates
0.371
Previous studies showed that casein kinase 1? (ck1?) Stably associates with mdmx, stimulates mdmx-p53 binding, and cooperates with mdmx to inactivate p53ck1? Binding to the mdmx central domain and phosphorylation of s289 disrupts the intramolecular interaction, allowing the n terminus to bind p53 with increased affinity. After dna damage, the mdmx-ck1? Complex is disrupted by chk2-mediated phosphorylation of mdmx at s367, leading to reduced mdmx-p53 binding.
SIGNOR-199015
P10415
P00441
2
binding
up-regulates activity
0.507
Familial amyotrophic lateral sclerosis (ALS)-linked mutations in the copper-zinc superoxide dismutase (SOD1) gene cause motor neuron death in about 3% of ALS cases. While the wild-type (wt) protein is anti-apoptotic, mutant SOD1 promotes apoptosis.|We now demonstrate that both wt and mutant SOD1 bind the anti-apoptotic protein Bcl-2, providing evidence of a direct link between SOD1 and an apoptotic pathway. This interaction is evident in vitro and in vivo in mouse and human spinal cord.|These findings provide new insights into the anti-apoptotic function of SOD1 and suggest that entrapment of Bcl-2 by large SOD1 aggregates may deplete motor neurons of this anti-apoptotic protein.
SIGNOR-262799
P29353
P62993
2
binding
up-regulates
0.965
TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases.
SIGNOR-236366
Q9Y463
Q9Y463
2
phosphorylation
up-regulates
0.2
Mirk kinase is activated by autophosphorylation on tyrosine at the y271/y273 site
SIGNOR-79810
Q9BXM7
O75439
0
cleavage
down-regulates quantity by destabilization
0.339
Using an unbiased RNA-mediated interference (RNAi)-based screen, we identified four mitochondrial proteases, mitochondrial processing peptidase (MPP), presenilin-associated rhomboid-like protease (PARL), m-AAA and ClpXP, involved in PINK1 degradation. We find that PINK1 turnover is particularly sensitive to even modest reductions in MPP levels. Moreover, PINK1 cleavage by MPP is coupled to import such that reducing MPP activity induces PINK1 accumulation at the mitochondrial surface, leading to Parkin recruitment and mitophagy.
SIGNOR-261363
P07948
P15391
2
phosphorylation
up-regulates
0.772
Experiments with purified proteins demonstrated that cd19-y513 was lyn's initial phosphorylation and binding site. This led to processive phosphorylation of cd19-y482, which recruited a second lyn molecule, allowing for transphosphorylation and amplification of lyn activation.
SIGNOR-80290
Q9ULB1
Q99767
2
binding
up-regulates activity
0.636
Mint1 and Mint2 Interact with the Cytoplasmic Domain of Neurexin I. The interaction of Mint1 with neurexins is mediated by its PDZ domains and allows the formation of mixed CASK-Mint complexes. Both CASK and Mint1 can bind directly to neurexins and to each other. Therefore, the assembly of various multimeric complexes could proceed as CASK could be indirectly recruited to neurexin-bound Mint1 and vice versa.
SIGNOR-264039
Q9UQM7
Q9NSC5
1
phosphorylation
down-regulates activity
0.2
Homer3 is phosphorylated at Ser120, Ser159, and Ser176 by CaMKII in vitro. Homer3 phosphorylation reduces its affinity for target molecules and modulates the Ca2+ signaling patterns induced by mGluR1α activation
SIGNOR-262685
Q99873
P62633
1
methylation
down-regulates
0.368
Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding
SIGNOR-204958
Q13163
Q9Y2U5
0
phosphorylation
up-regulates
0.762
Mekk2 and mekk3 are mapk kinase kinases that bind, phosphorylate and activate mek5.
SIGNOR-104634
Q9UGP8
Q99442
2
binding
up-regulates activity
0.96
Sec63 was identified as a novel substrate and binding partner of protein kinase CK2. We identified serine 574, serine 576 and serine 748 as CK2 phosphorylation sites. Phosphorylation of Sec63 by CK2 enhanced its binding to Sec62.
SIGNOR-265273
P24385
Q8N3Y1
2
binding
down-regulates quantity by destabilization
0.511
We next investigated whether in vitro ubiquitination of cyclin D1 through the SCF-like (SCFL) complex FBXW8 (SKP1-CUL7-FBXW8-RBX1/SCFLFBXW8) requires phosphorylation of cyclin D1 at Thr286 (Fig. 3F). Polyubiquitination through SCFLFBXW8 was dramatically reduced by the depletion of ERK2 (lane 2). Furthermore, cyclin D1 polyubiquitination was largely prevented by the alanine-for-Thr286 substitution (T286A, lane 3), suggesting that phosphorylation of cyclin D1 at Thr286 is necessary for ubiquitination by SCFLFBXW8.
SIGNOR-271624
P26045
P55072
1
dephosphorylation
down-regulates activity
0.478
Identification of VCP as a substrate of PTPH1in vivo.|The tyrosines (Tyr796 and Tyr805) at the C terminus of VCP have been reported to be the major sites of phosphorylation, with Tyr805 accounting for more than 90% of the tyrosine phosphorylation on the protein |The Y796F/Y805F VCP mutant was not associated with any of the PTPH1 constructs.
SIGNOR-248460
P62195
Q15751
0
ubiquitination
down-regulates quantity
0.2
HERC1 interacts with and ubiquitinates nascent PSMC5.|PSMC5 produced in the absence of PAAF1 is presumably misfolded (consistent with its aggregation in the PURE system), triggering PSMC5 degradation by a HERC1-independent pathway.
SIGNOR-278812
P24385
O15111
0
phosphorylation
down-regulates
0.379
Ikkalpha regulates subcellular localization and proteolysis of cyclin d1 by phosphorylation of cyclin d1 at thr286.
SIGNOR-139570
P43699
P84022
2
binding
down-regulates activity
0.29
TGF-beta represses transcription of pulmonary surfactant protein-B gene in lung epithelial cells. Repression is mediated by SMAD3 through interactions with NKX2.1 and FOXA1, two key transcription factors that are positive regulators of SpB transcription. In this study, we found that SMAD3 interacts through its MAD domains, MH1 and MH2 with NKX2.1 and FOXA1 proteins. The sites of interaction on NKX2.1 are located within the NH2 and COOH domains, known to be involved in transactivation function.
SIGNOR-254169
P85298
P45983
0
phosphorylation
up-regulates activity
0.327
Furthermore, we identify that BPGAP1 (a BCH domain-containing, Cdc42GAP-like Rho GTPase-activating protein) promotes MEK partner 1 (MP1)-induced ERK activation on late endosome through scaffolding MP1/MEK1 complex. This regulatory function requires phosphorylation of BPGAP1 by JNK at its C terminal tail (Ser424) to unlock its autoinhibitory conformation.
SIGNOR-275550
P61073
Q15139
0
phosphorylation
down-regulates quantity
0.2
Inhibition of PKD activity restores membrane expression of CXCR4 and migration towards CXCL12 in BCR responsive cells in vitro.|This cascade consisted on a novel BCR dependent pathway in which PI3K-delta phosphorylates PKD, which in turn phosphorylates CXCR4 at Ser 324/325.
SIGNOR-279263
P20823
Q13315
0
phosphorylation
up-regulates
0.256
Serine 249 phosphorylation by atm protein kinase regulates hepatocyte nuclear factor-1_ transactivation
SIGNOR-205087
Q15118
P29803
1
phosphorylation
down-regulates
0.505
Human pdh1 and rat pdh2 were expressed previously and were shown to have different specific activities and the ability to be phosphorylated by pdk1 and pdk2
SIGNOR-143966
P40189
P20809
2
binding
up-regulates
0.714
Some of these biological activities of il-6 are also often exerted by other cytokines, i.e. Il-11, lif, osm, cntf, and ct-4
SIGNOR-48033
Q01105
Q9BZL6
0
phosphorylation
down-regulates activity
0.2
In conclusion, the roles of protein kinase D2 and its substrate SET in T cell activation were investigated and we found that protein kinase D2 phosphorylates Ser171 of SET, which resulted in the reduction of its inhibitory effect on PP2A phosphatase activity.
SIGNOR-279560
P68400
Q96G74
1
phosphorylation
up-regulates activity
0.2
Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. Treatment with CK2 could activate DUBA purified from E. coli, and this activity was associated with a species monophosphorylated at Ser177 (Fig. 1d).
SIGNOR-265872
O95166
Q8IZQ1
2
binding
down-regulates quantity by destabilization
0.661
Here, we show that ALFY binds selectively to LC3C and the GABARAPs through a LIR in its WD40 domain. Binding of ALFY to GABARAP is indispensable for its recruitment to LC3B-positive structures and, thus, for the clearance of certain p62 structures by autophagy.
SIGNOR-266796
P63092
P46663
2
binding
up-regulates activity
0.25
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 ‚â• -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 ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.
SIGNOR-256764
O00220
P50591
2
binding
up-regulates
0.934
Trail interacts with tril-r1 and trail-r2 and activetes them
SIGNOR-101082
P01116
P04049
2
binding
up-regulates
0.847
Among other effectors, active ras binds and activates the raf kinase, iniziating a kinase cascade involving serine phosporylation of mek1/2 (mapkk) and tyrosine and threonine phosphorylation of erk1/2. the raf family of proteins (raf-1, a-raf, and b-raf) is serine/threonine kinases that bind to the effector region of ras-gtp, thus inducing translocation of the protein to the plasma membrane. Once there, raf proteins are activated and phosphorylated by different protein kinases.. Association of ras with the mapk kinase kinase, raf, initiates the raf mek erk map kinase cascade.
SIGNOR-78911
P52738
O75015
1
transcriptional regulation
down-regulates quantity by repression
0.2
Thus, these results indicate that these cloned ZNF140 and ZNF91 proteins function as repressors for the human Fc gamma RIIB transcription.
SIGNOR-266214
Q15628
P02533
2
binding
down-regulates activity
0.346
TRADD specifically bound K18 and K14, type I (acidic) keratins. it is possible that epidermal K14 may function as an inhibitor of TNF–TNFR1 signaling through an association with TRADD.
SIGNOR-251907
Q9Y5H9
Q9Y5H0
2
binding
up-regulates activity
0.2
The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.
SIGNOR-265677
P31391
P61278
2
binding
up-regulates
0.777
The five receptor subtypes bind the natural SST peptides, SST-14 and SST-28, with low nanomolar affinity.
SIGNOR-82496
Q13164
P17302
1
phosphorylation
down-regulates activity
0.54
Activated BMK1 selectively phosphorylates Cx43 on Ser-255 in vitro and in vivo. These data demonstrate that BMK1 kinase activity alone is both a necessary and sufficient component in the mediation of EGF-induced Cx43 Ser-255 phosphorylation and subsequent inhibition of GJC.
SIGNOR-250115
P62979
P15374
0
cleavage
up-regulates quantity
0.802
Here we provide data suggesting that two of the four mammalian ubiquitin precursors, UBA52 and UBA80, are processed mostly post-translationally whereas the other two, UBB and UBC, probably undergo a combination of co- and post-translational processing. Using an unbiased biochemical approach we found that UCHL3, USP9X, USP7, USP5 and Otulin/Gumby/FAM105b are by far the most active DUBs acting on these precursors.
SIGNOR-270828
Q8TEW6
P46108
2
binding
up-regulates
0.46
Insulin receptor-phosphorylated irs5/dok4 associates with rasgap, crk, src, and fyn, but not phosphatidylinositol 3-kinase p85, grb2, shp-2, nck, or phospholipase cgamma src homology 2 domains, and activates mapk in cells.
SIGNOR-100996
P08243
Q02447
0
transcriptional regulation
up-regulates quantity by expression
0.2
Sp1 and Sp3 Activate Transcription Driven by the AS Promoter
SIGNOR-268020
Q96J02
Q8NFZ5
1
ubiquitination
down-regulates
0.268
Here we show that tnfa-mediated jnk activation accelerates turnover of the NF-kappaBinduced antiapoptotic protein c-flip, an inhibitor of caspase-8. This is not due to direct c-flip phosphorylation but depends on jnk-mediated phosphorylation and activationof the e3ubiquitin ligaseitch, which speci?cally Ubiquitinates c-flip and induces its proteasomal degradation.
SIGNOR-144453
P78527
P42575
1
phosphorylation
up-regulates
0.297
Here we show that dna damage induced by gamma-radiation triggers the phosphorylation of nuclear caspase-2 at the s122 site within its prodomain, leading to its cleavage and activation. This phosphorylation is carried out by the nuclear serine/threonine protein kinase dna-pkcs
SIGNOR-183895
A6ND36
Q8N752
2
binding
up-regulates quantity
0.337
We identified members of the FAM83 family of proteins as partners of CK1 in cells. All eight members of the FAM83 family (FAM83A–H) interacted with the α and α-like isoforms of CK1; FAM83A, -B, -E, and -H also interacted with the δ and ε isoforms of CK1. The intrinsic catalytic activity of CK1 is not affected by or required for the association of CK1 with FAM83 proteins. Our findings imply that the DUF1669 domains of FAM83 proteins anchor CK1 α, α-like, δ, and ε isoforms in specific subcellular compartments and potentially mediate their association with substrates.
SIGNOR-273753
P17612
Q00536
1
phosphorylation
down-regulates
0.314
Here, we report that cdk16 is activated by membrane-associated cyclin y (ccny). Treatment of transfected human cells with the protein kinase a (pka) activator forskolin blocked, while kinase inhibition promoted, ccny-dependent targeting of cdk16-green fluorescent protein (gfp) to the cell membrane. Ccny binding to cdk16 required a region upstream of the kinase domain and was found to be inhibited by phosphorylation of serine 153, a potential pka phosphorylation site.
SIGNOR-191623
P20333
Q12933
2
binding
up-regulates activity
0.708
Our analysis indicates that traf1 and traf2 are associated with the cytoplasmic domain of tnf-r2 in a heterodimeric complex in which traf2 contacts the receptor directly.
SIGNOR-34645
Q9HAW4
O00311
0
phosphorylation
up-regulates activity
0.742
Cdc7 phosphorylates Claspin in a manner dependent on AP and inhibits N\u2013C interaction.|Thus, Cdc7-ASK may activate DNA and PCNA bindings of Claspin through AP-mediated phosphorylation.
SIGNOR-279360
P53396
P07948
0
phosphorylation
up-regulates activity
0.2
 We demonstrate the binding of PIP2 to the CoA-binding domain of ACLY and identify the six tyrosine residues of ACLY that are phosphorylated by Lyn. Three of them (Y682, Y252, Y227) can be also phosphorylated by Src and they are located in catalytic, citrate binding and ATP binding domains, respectively. PI3K and Lyn inhibitors reduce the ACLY enzyme activity, ACLY-mediated Acetyl-CoA synthesis, phospholipid synthesis, histone acetylation and cell growth. Thus, PIP2/PIP3 binding and Src tyrosine kinases-mediated stimulation of ACLY links oncogenic pathways to Acetyl-CoA-dependent pro-growth and survival metabolic pathways in cancer cells.
SIGNOR-274105
P45985
Q9Y2U5
0
phosphorylation
up-regulates activity
0.612
Both mekk2 and mekk3 are able to activate the jun kinase pathway in vivo. However, following routine immunoprecipitation in triton x-100, mekk2 but not mekk3 is able to effectively phosphorylate both sek-1 and mek-1 and to undergo autophosphorylation
SIGNOR-107695
Q06413
Q9UPW0
0
transcriptional regulation
up-regulates quantity by expression
0.317
Foxj3 transcriptionally activates Mef2c and regulates adult skeletal muscle fiber type identity.
SIGNOR-261606
Q969H0
P31749
0
phosphorylation
up-regulates activity
0.41
A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.
SIGNOR-276328
P08754
P21453
2
binding
up-regulates activity
0.504
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-256856
Q02962
Q6ZW49
2
binding
up-regulates activity
0.571
PTIP promotes assembly of the ALR complex and H3K4 methylation at a PAX2-binding DNA element. Without PTIP, Pax2 binds to this element but does not assemble the ALR complex
SIGNOR-251711
Q14344
O15552
2
binding
up-regulates activity
0.2
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- 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-257397
Q96EP5
P28482
0
phosphorylation
down-regulates activity
0.2
Further experiments showed that DAZAP1 was phosphorylated stoichiometrically in vitro by ERK2 (extracellular-signal-regulated protein kinase 2) at two Thr-Pro sequences (Thr269 and Thr315), and that both sites became phosphorylated in HEK-293 (human embryonic kidney 293) cells in response to PMA or EGF (epidermal growth factor), or RAW 264.7 macrophages in response to LPS. Phosphorylation of the ARE-binding protein DAZAP1 by ERK2 induces its dissociation from DAZ
SIGNOR-262970
P17542
P17947
2
binding
down-regulates activity
0.439
PU.1/Spi-1 binds to the human TAL-1 silencer to mediate its activity.By expressing a mutant protein containing only the ETS domain of PU.1 in human erythroleukemic HEL cells, we demonstrated that PU.1 mediates the transcriptional repression activity of the silencer. Our data clearly demonstrate that PU.1 mediates TAL-1 silencer activity
SIGNOR-256048
Q9Y2T4
P12931
2
binding
down-regulates activity
0.2
We show that PR55gamma binds c-SRC and modulates the phosphorylation of serine 12 of c-SRC, a residue we demonstrate to be required for JNK activation by c-SRC
SIGNOR-247966
P24844
O43293
0
phosphorylation
up-regulates
0.487
More than a dozen kinases have been reported to phosphorylate the rlcs of nm ii (fig. 2), including myosin light chain kinase (mlck;also known as mylk), rho-associated, coiled coil-containing kinase (rock), citron kinase, leucine zipper interacting kinase (zipk;also known as dapk3) and myotonic dystrophy kinase-related cdc42-binding kinase (mrck;also known as cdc42bp)6,34,45,46. These kinases phosphorylate rlcs on ser19, thr18 or both, to relieve the inhibition imposed on the myosin molecule by unphosphorylated rlcs and the head_head interaction outlined above.
SIGNOR-188789
Q9Y5H9
Q9Y5G2
2
binding
up-regulates activity
0.2
The clustered protocadherins comprise the largest subfamily of the cadherin superfamily and are predominantly expressed in the nervous system. Pcdh-alpha proteins interact with beta1-integrin to promote cell adhesion. They also form oligomers with Pcdh-gamma proteins at the same membrane sites.
SIGNOR-265688
Q8IXT1
Q9UNE7
0
ubiquitination
down-regulates quantity by destabilization
0.322
HSP70 recruits DDIAS to the CHIP E3 ligase, whereas CHIP promotes the ubiquitination of DDIAS.|However, the findings clearly demonstrated that HSP70 was solely involved in CHIP mediated proteasomal degradation of DDIAS.
SIGNOR-278784
O14786
Q13214
2
binding
up-regulates activity
0.753
Further examination of the composition of the functional Sema3B receptor revealed that, unlike Sema3A, which signals exclusively using the NP1 receptor, Sema3B utilizes both NP1 and NP2 for signal transduction.
SIGNOR-261814
Q92793
Q04206
2
acetylation
up-regulates
0.879
Rela is also acetylated at several sites by p300 and cbp
SIGNOR-143396
Q04206
O14757
0
phosphorylation
up-regulates activity
0.454
Here we demonstrate that ARF induces the ATR- and Chk1-dependent phosphorylation of the RelA transactivation domain at threonine 505, a site required for ARF-dependent repression of RelA transcriptional activity.
SIGNOR-280225
Q13148
Q9H2K2
2
binding
up-regulates quantity by stabilization
0.2
Upon investigating the functional effect, we find that interaction with Tnks-1/2 inhibits the ubiquitination and proteasomal turnover of TDP-43, leading to its stabilization. We further show that proteasomal turnover of TDP-43 occurs preferentially in the nucleus; our data indicate that Tnks-1/2 stabilizes TDP-43 by promoting cytoplasmic accumulation, which sequesters the protein from nuclear proteasome degradation.
SIGNOR-262116
P32238
P08754
2
binding
up-regulates activity
0.252
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-257148