GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P31749	Q969V5	ubiquitination	down-regulates quantity by destabilization	0.475	The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.	SIGNOR-252437
P01579	Q9UL17	transcriptional regulation	up-regulates quantity by expression	0.475	T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells	SIGNOR-266234
O43524	Q8IW41	phosphorylation	up-regulates activity	0.475	Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).\|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors.	SIGNOR-279469
P10415	O75030	transcriptional regulation	up-regulates quantity by expression	0.475	MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF	SIGNOR-249618
Q99986	Q9H4B4	phosphorylation	up-regulates	0.474	Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.	SIGNOR-182858
P20749	P28482	phosphorylation	up-regulates activity	0.474	Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.	SIGNOR-277361
P29590	Q13164	phosphorylation	down-regulates activity	0.474	Big MAP kinase 1 (BMK1) also phosphorylates PML at two sites : S403 and T409.\|Mutational analysis demonstrated that BMK1 drives suppression of PML directly through its phosphorylation.	SIGNOR-279074
P37275	Q13315	phosphorylation	up-regulates activity	0.474	Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation.\|Therefore, ATM dependent phosphorylation of ZEB1 at S585 is crucial for IR induced stabilization of ZEB1 but not the interaction between ZEB1 and USP7.	SIGNOR-278329
Q15722	P43250	phosphorylation	down-regulates activity	0.474	Thr(308) is a major residue involved in GRK6-mediated desensitization of BLT1 signaling.	SIGNOR-251213
P41968	Q8TCY5	binding	down-regulates activity	0.474	We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.	SIGNOR-252366
P04637	P53778	phosphorylation	up-regulates activity	0.474	Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.	SIGNOR-280026
Q13568	O15111	phosphorylation	down-regulates activity	0.474	These data indicate that in context of MyD88 signaling pathway IKKalpha suppresses IRF-5 activation.\|These data showed that the IKK\u03b1 phosphorylates IRF-5 and that IKK\u03b1 mediated phosphorylation stimulates formation of IRF-5 dimers.	SIGNOR-278293
Q15796	Q13233	phosphorylation	up-regulates activity	0.474	As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.\|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .	SIGNOR-279064
Q99708	Q96M94	binding	down-regulates quantity by destabilization	0.474	Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway.	SIGNOR-272410
Q5FWF5	P06493	phosphorylation	down-regulates	0.474	We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases , cdc7-dbf4 and the gsk-3 homolog mck1.	SIGNOR-200400
P49792	P06493	phosphorylation	up-regulates activity	0.474	Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment.	SIGNOR-259118
O60675	O14867	binding	up-regulates activity	0.474	Bach1 forms a heterodimer with the small Maf oncoproteins and binds to the Maf-recognition element (MARE) to inhibit target genes	SIGNOR-226409
Q12837	Q8N100	transcriptional regulation	up-regulates quantity by expression	0.474	Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.	SIGNOR-261567
Q9H8V3	P41743	phosphorylation	up-regulates	0.474	Our data support a model in which pkc?-Mediated phosphorylation regulates ect2 binding to the oncogenic pkc?-Par6 complex thereby activating rac1 activity and driving transformed growth and invasion.	SIGNOR-170790
P50148	P30968	binding	up-regulates activity	0.474	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-257265
P50148	Q92847	binding	up-regulates activity	0.474	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-257380
P04234	Q9UKV5	polyubiquitination	down-regulates quantity by destabilization	0.474	Gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate.	SIGNOR-272670
P49795	P28482	phosphorylation	up-regulates	0.474	Phosphorylation of gaip by erk2 were abrogated when serine at position 151 in the rgs domain was substituted by an alanine residue using site-directed mutagenesis. Furthermore, the lysosomal-autophagic pathway was not stimulated in s151a-gaip mutant-expressing cells when compared with wild-type gaip-expressing cells. These results demonstrate that the gtpase-activating protein activity of gaip is stimulated by erk2 phosphorylation.	SIGNOR-129883
O14920	O15530	phosphorylation	up-regulates activity	0.474	We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression.	SIGNOR-279088
Q9H1E3	P06493	phosphorylation	down-regulates activity	0.474	putative phosphorylation site for Cdk1 is present in the DNA-binding domain peptide. This site, corresponding to Ser 181 in the NUCKS primary structure, is phosphorylated in vitro by Cdk1 with a Km of approximately 35 μM [7]. Phosphorylation of Ser 181 in the synthetic, DNA-binding domain peptide reduces its affinity for DNA-by 100%.	SIGNOR-261959
P42338	P46109	binding	up-regulates activity	0.474	Here, we identify CRKL as a member of the class of PI3Kβ-interacting proteins. Silencing CRKL expression in PTEN-null human cancer cells leads to a decrease in p110β-dependent PI3K signaling and cell proliferation.In conclusion, our study identified CRKL as an important regulator of PI3K activity in PTEN-deficient tumor cells through its association with p110β/p85.	SIGNOR-255821
P36956	P49336	phosphorylation	up-regulates activity	0.474	Biochemical analyses reveal that SREBP-1c can be directly phosphorylated by CDK8 at the conserved Threonine-402 residue (T402) in vitro and in cultured mammalian cells ( xref ).\|Therefore, the mechanism of CDK8 regulating SREBP functions is primarily through the phosphorylation initiated control of nuclear SREBP-1 protein stability.	SIGNOR-279688
P60568	Q9UL17	transcriptional regulation	down-regulates quantity by repression	0.473	T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells	SIGNOR-266233
O14757	O15297	dephosphorylation	down-regulates activity	0.473	Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity.	SIGNOR-248317
P05106	O15530	phosphorylation	down-regulates activity	0.473	PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.	SIGNOR-250266
Q9HCU9	P68400	phosphorylation	down-regulates quantity by destabilization	0.473	We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation.	SIGNOR-266407
P38398	P42574	cleavage	down-regulates quantity by destabilization	0.473	We demonstrate the cleavage and the consequential downregulation of full-length BRCA1 by caspase-3 during UV-induced apoptosis. Finally, mutation of a caspase-3 specific cleavage site (D/A1154) rendered BRCA1 non-cleavable.	SIGNOR-256326
O14641	Q9Y2G4	binding	up-regulates	0.473	Our data thus demonstrate that diversin and dishevelled function together in a mutually dependent fashion in zebrafish gastrulation and organ formation	SIGNOR-162142
Q9BQE3	Q8NG68	tyrosination	down-regulates	0.473	Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization	SIGNOR-176918
Q12972	P19784	phosphorylation	up-regulates activity	0.473	Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2.	SIGNOR-251023
Q8NFZ4	Q9NQX3	binding	up-regulates activity	0.473	Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and collybistin, suggesting that it may be critical for the maturation or maintenance of inhibitory synapses.	SIGNOR-264974
P15311	O94804	phosphorylation	up-regulates activity	0.473	Ezrin activation by LOK phosphorylation involves a PIP 2 -dependent wedge mechanism.\|The specificity of kinases depends on local peptide consensus sequences, which in the case of ezrin phosphorylation by LOK involves the hydrophobic residue Y565 positioned -2 residues from T567.	SIGNOR-278204
P78352	Q06787	post transcriptional regulation	up-regulates quantity	0.473	These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.	SIGNOR-262108
Q12904	P45983	phosphorylation	down-regulates	0.473	We further demonstrated that serine-140 residue of aimp1 was phosphorylated by jnk and alanine mutation of serine-140 suppressed lps-induced cell surface altogether, these results suggest that aimp1 is phosphorylated by jnk through tlr-myd88 pathway and lose the regulatory activity for er retention of gp96expression of gp96.	SIGNOR-165763
O75525	Q8IUQ4	polyubiquitination	down-regulates quantity by destabilization	0.473	We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation.	SIGNOR-272671
P45984	P52564	phosphorylation	up-regulates	0.473	A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)	SIGNOR-45369
P10415	O00198	binding	down-regulates	0.472	Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1.	SIGNOR-47794
O60674	P08575	dephosphorylation	down-regulates activity	0.472	Src homology-2 (SH2) containing tyrosine phosphatase and CD45 tyrosine phosphatase play a major role in modulating JAK-STAT pathway. SH2 containing tyrosine phosphatases include SHP1 and SHP2 (shatterproof 1 & 2). Their SH2 domains allow attachment to the phospho-tyrosine residues present on activated receptors, JAKs or STAT proteins, leading to dephosphorylation of the substrates.	SIGNOR-255679
P50148	P28336	binding	up-regulates	0.472	G-proteins of the q family have been implicated as mediators of bombesin receptors action. This suggests that nmb-r couples to g?q, and that grp-r and nmb-r show distinct g-protein coupling preferences in the xenopus oocyte.	SIGNOR-35864
Q9NYV6	P45984	phosphorylation	down-regulates	0.472	Inactivation is due to phosphorylation of tif-ia by c-jun n-terminal kinase (jnk) at a single threonine residue (thr 200). Phosphorylation at thr 200 impairs the interaction of tif-ia with pol i and the tbp-containing factor tif-ib/sl1, thereby abrogating initiation complex formation.	SIGNOR-134878
P63096	P47211	binding	up-regulates activity	0.472	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-256687
Q99962	Q5S007	phosphorylation	down-regulates	0.472	We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75.	SIGNOR-192072
Q9UPY8	Q96GD4	phosphorylation	up-regulates	0.472	Phosphorylation of eb3 at s176 by aurora b ensures successful cytokinesis completion by promoting midbody mt stability and midbody stabilization.	SIGNOR-202130
P78352	Q5JU85	relocalization	up-regulates activity	0.472	Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.	SIGNOR-264907
Q9Y4K3	Q86UT6	binding	down-regulates activity	0.472	Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.	SIGNOR-260364
P49675	Q13285	transcriptional regulation	up-regulates quantity by expression	0.472	The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.	SIGNOR-271788
O75886	P18031	dephosphorylation	up-regulates quantity by stabilization	0.472	Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.	SIGNOR-248406
P05305	P23946	cleavage	up-regulates activity	0.472	Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products.	SIGNOR-256356
Q13501	Q14596	binding	up-regulates	0.472	Nbr1 and p62 interact and form oligomers.	SIGNOR-184273
Q12959	P11171	relocalization	up-regulates activity	0.472	Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.	SIGNOR-266011
P08514	Q99828	binding	up-regulates activity	0.472	The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading	SIGNOR-269061
Q92934	Q08209	dephosphorylation	up-regulates activity	0.471	Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD\|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.	SIGNOR-248694
P35222	P19784	phosphorylation	up-regulates quantity by stabilization	0.471	We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin.	SIGNOR-275993
P04629	P51149	binding	down-regulates activity	0.471	Endogenous TrkA and Rab7 form a complex. Inhibition of Rab7 potentiates the signaling of TrkA in response to brief stimulations with NGF	SIGNOR-261305
Q9C0C7	P42345	phosphorylation	down-regulates activity	0.471	We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.\|mTOR phosphorylates AMBRA1 at Ser 52, inhibiting its role in ULK1 modification	SIGNOR-272986
Q13753	P08253	cleavage	up-regulates activity	0.471	Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5\|MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.	SIGNOR-253240
Q12972	P68400	phosphorylation	up-regulates activity	0.471	Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2.	SIGNOR-250931
Q16819	Q99626	transcriptional regulation	up-regulates quantity by expression	0.471	TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis\|	SIGNOR-253965
P13569	Q9UNE7	polyubiquitination	down-regulates quantity by destabilization	0.471	Here we show that CHIP functions with Hsc70 to sense the folded state of CFTR and targets aberrant forms for proteasomal degradation by promoting their ubiquitination.	SIGNOR-272584
Q92847	O00230	binding	up-regulates	0.471	In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).	SIGNOR-91134
P50148	P30989	binding	up-regulates activity	0.471	Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways	SIGNOR-278058
Q6NUQ1	Q92878	binding	up-regulates activity	0.471	We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.	SIGNOR-265030
P28069	P78337	binding	up-regulates activity	0.471	A novel OTX-related homeodomain transcription factor has been identified on the basis of its ability to interact with the transactivation domain of the pituitary-specific POU domain protein, Pit-1. P-OTX is able to independently activate and to synergize with Pit-1 on pituitary-specific target gene promoters.	SIGNOR-219740
P23560	P51608	transcriptional regulation	down-regulates quantity by repression	0.471	We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene.	SIGNOR-264540
P29475	Q9UQM7	phosphorylation	down-regulates activity	0.471	It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.	SIGNOR-250635
O14965	Q96EP1	polyubiquitination	down-regulates quantity by destabilization	0.471	Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.	SIGNOR-271463
P02647	Q8IZY2	binding	up-regulates activity	0.471	ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. HEK293 cells overexpressing ABCA7 showed specific binding and cross-linking of lipid-poor apoA-I. ABCA7 expression increased cellular phosphatidylcholine and sphingomyelin efflux to apoA-I in a manner similar to ABCA1 but had no effect on cholesterol efflux.	SIGNOR-265178
P63096	P49286	binding	up-regulates activity	0.471	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-256707
P05106	Q03405	binding	up-regulates activity	0.471	Recent evidence suggests that the activation of b3 integrin in podocytes mediates uPAR-induced cellular events leading to proteinuria	SIGNOR-253333
O95837	P25101	binding	up-regulates activity	0.471	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-257427
Q06124	P48357	binding	up-regulates activity	0.471	Because the long leptin receptor lacking tyrosine 985 exhibits a significantly reduced ability to activate ERK phosphorylation, this residue is at least in part mediating stimulation of the ERK pathway by ObRb. This residue binds SHP-2 and is required for tyrosine phosphorylation of SHP-2	SIGNOR-263506
P20273	P15907	glycosylation	down-regulates activity	0.471	CD22-ligand interaction is regulated by the activity of a b-galactoside a2,6- sialyltransferase that can inactivate CD22-mediated binding by sialylating the CD22 receptor itself. These observations suggest that N-linked glycosylation sites on the CD22 molecule may play a role in the regulation of CD22-mediated adhesion.	SIGNOR-261741
O14579	Q96PM5	polyubiquitination	down-regulates quantity by destabilization	0.471	PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP.	SIGNOR-272630
P67809	P28482	phosphorylation	up-regulates activity	0.47	ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.	SIGNOR-279227
Q15645	Q15013	binding	up-regulates activity	0.47	We have indeed showed that TRIP13 action to disassemble the Cdc20–Mad2 complex requires the presence of p31comet (Fig. 3A). We furthermore found that the joint action of TRIP13 and p31comet is also required for the release of Mad2 from MCC, for the complete disassembly of MCC and for relieving APC/C from checkpoint inhibition (Figs. 3 and and4).4).	SIGNOR-265971
P02511	P04637	transcriptional regulation	up-regulates quantity by expression	0.47	Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously\|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53	SIGNOR-253638
Q03113	O95136	binding	up-regulates	0.47	Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.	SIGNOR-198556
Q8NE35	O76050	ubiquitination	up-regulates activity	0.47	If Neurl1 interacts and modulates the activity of CPEB3 and increases the translation of GluA1 and GluA2 mRNAs, this effect would be blocked if we abolished the interaction between CPEB3 and Neurl1.\|Neurl1 Interacts with and Ubiquitinates a Translational Regulator of GluA1 and GluA2 : the Cytoplasmic Polyadenylation Element Binding Protein 3.	SIGNOR-278588
P35712	Q9BS16	binding	up-regulates activity	0.47	Here we report the cloning of a novel cDNA, termed Solt, from a mouse testis cDNA library. Its gene product, Solt, interacts with the leucine zipper region of SoxLZ/Sox6. In transient transfection assays with SoxLZ/Sox6 containing the transactivation domain of herpes simplex virus VP16, the expression of a luciferase reporter gene under the control of a promoter containing a synthetic cis element that is bound by the HMG box of SoxLZ/Sox6 was poorly enhanced in the presence of Solt.	SIGNOR-221820
Q14194	P49841	phosphorylation	up-regulates	0.47	Using in vitro kinase assays and pharmacological inhibition of gsk3 as described above for crmp2 and crmp4, it was found that thr509 (and presumably ser518 and thr514) of human crmp1 is phosphorylated by gsk3, following priming of ser522 by cdk5	SIGNOR-145999
P60484	Q9BXM7	phosphorylation	down-regulates activity	0.47	PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import.	SIGNOR-277915
P63000	Q8WWN8	gtpase-activating protein	down-regulates activity	0.47	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-260456
P48506	Q16236	transcriptional regulation	up-regulates quantity by expression	0.47	In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).	SIGNOR-256277
Q9NZQ7	Q9NX76	stabilization	up-regulates quantity by stabilization	0.47	Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation	SIGNOR-274980
P40763	Q9Y4K3	ubiquitination	down-regulates activity	0.47	TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.\|TRAF6 Represses the Transcriptional Activity of STAT3.	SIGNOR-278618
O14974	O95835	phosphorylation	up-regulates activity	0.47	LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.\|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.	SIGNOR-278184
P03372	O15111	phosphorylation	up-regulates activity	0.47	These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).\|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation.	SIGNOR-279696
P10415	P67775	dephosphorylation	up-regulates activity	0.47	The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.	SIGNOR-248624
O15078	Q7Z7A1	binding	down-regulates activity	0.47	CEP290 cooperates with Rab8a to promote ciliogenesis and this function is antagonized by CP110. CP110 in this complex is to keep CEP290 inactive in growing cells until cells are ready to undergo ciliogenesis as they transit into the quiescent state	SIGNOR-252149
P35241	P61586	phosphorylation	up-regulates activity	0.47	Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.	SIGNOR-268430
P42356	Q14156	binding	up-regulates quantity	0.47	PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B	SIGNOR-269092
P63000	P63096	binding	up-regulates activity	0.47	These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin	SIGNOR-256530
Q9UPT9	P06493	phosphorylation	up-regulates activity	0.47	On the other hand, CDK1 enhances USP22 activity to stabilize CCNB1 during the G2/M phase.\|Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1.	SIGNOR-278241
O95837	P21731	binding	up-regulates activity	0.47	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-257023
P08754	P18089	binding	up-regulates activity	0.47	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-256857

P31749

Q969V5

0

ubiquitination

down-regulates quantity by destabilization

0.475

The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability.

SIGNOR-252437

P01579

Q9UL17

0

transcriptional regulation

up-regulates quantity by expression

0.475

T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells

SIGNOR-266234

O43524

Q8IW41

0

phosphorylation

up-regulates activity

0.475

Analysis of mutant alleles of FoxO3a showed that MK5 phosphorylated FoxO3a predominantly at S215, but that mutation of four of the identified sites was required to essentially abolish phosphorylation of FoxO3a by MK5 (\u201c4A\u201d) ( Figure\u00a04 C and data not shown).|MK5 phosphorylates and activates the transcription factor FoxO3a and potentially other FoxO factors.

SIGNOR-279469

P10415

O75030

0

transcriptional regulation

up-regulates quantity by expression

0.475

MITF directly occupies the BCL2 promoter in vivo and this suggest that BCL2 may be a direct transcriptional target of MITF

SIGNOR-249618

Q99986

Q9H4B4

0

phosphorylation

up-regulates

0.474

Vrk1 does not phosphorylate plk3, but plk3 phosphorylates the c-terminal region of vrk1 in ser342. Vrk1 with substitutions in s342 is catalytically active but blocks golgi fragmentation, indicating that its specific phosphorylation is necessary for this process.

SIGNOR-182858

P20749

P28482

0

phosphorylation

up-regulates activity

0.474

Here we show that Akt, Erk2, and IKK1/2 phosphorylate Bcl3. Phosphorylation of Ser33 by Akt induces switching of K48 ubiquitination to K63 ubiquitination and thus promotes nuclear localization and stabilization of Bcl3. Phosphorylation by Erk2 and IKK1/2 of Ser114 and Ser446 converts Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA.

SIGNOR-277361

P29590

Q13164

0

phosphorylation

down-regulates activity

0.474

Big MAP kinase 1 (BMK1) also phosphorylates PML at two sites : S403 and T409.|Mutational analysis demonstrated that BMK1 drives suppression of PML directly through its phosphorylation.

SIGNOR-279074

P37275

Q13315

0

phosphorylation

up-regulates activity

0.474

Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation.|Therefore, ATM dependent phosphorylation of ZEB1 at S585 is crucial for IR induced stabilization of ZEB1 but not the interaction between ZEB1 and USP7.

SIGNOR-278329

Q15722

P43250

0

phosphorylation

down-regulates activity

0.474

Thr(308) is a major residue involved in GRK6-mediated desensitization of BLT1 signaling.

SIGNOR-251213

P41968

Q8TCY5

0

binding

down-regulates activity

0.474

We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members.

SIGNOR-252366

P04637

P53778

0

phosphorylation

up-regulates activity

0.474

Furthermore, upon activation by oncogenic ras, p38gamma stimulated the transcriptional activity of p53 by phosphorylating p53 at Ser(33), suggesting that the ability of p38gamma to mediate senescence is at least partly achieved through p53.

SIGNOR-280026

Q13568

O15111

0

phosphorylation

down-regulates activity

0.474

These data indicate that in context of MyD88 signaling pathway IKKalpha suppresses IRF-5 activation.|These data showed that the IKK\u03b1 phosphorylates IRF-5 and that IKK\u03b1 mediated phosphorylation stimulates formation of IRF-5 dimers.

SIGNOR-278293

Q15796

Q13233

0

phosphorylation

up-regulates activity

0.474

As yet, the apparent discrepancy between these and above data is not clear, but obviously the type of cell under study and the cellular context may play an important role.In endothelial cells, Smad2 activity is stimulated by MEKK1, a component of the Stress Activated Protein Kinase and c-Jun N terminal kinase (SAPK and JNK) pathway.|Phosphorylation of Smad2 by MEKK1 increased its association with Smad4, its nuclear accumulation and its transcription induction activity .

SIGNOR-279064

Q99708

Q96M94

0

binding

down-regulates quantity by destabilization

0.474

Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway.

SIGNOR-272410

Q5FWF5

P06493

0

phosphorylation

down-regulates

0.474

We show here that eco1 degradation requires the sequential actions of cdk1 and two additional kinases , cdc7-dbf4 and the gsk-3 homolog mck1.

SIGNOR-200400

P49792

P06493

0

phosphorylation

up-regulates activity

0.474

Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment.

SIGNOR-259118

O60675

O14867

0

binding

up-regulates activity

0.474

Bach1 forms a heterodimer with the small Maf oncoproteins and binds to the Maf-recognition element (MARE) to inhibit target genes

SIGNOR-226409

Q12837

Q8N100

0

transcriptional regulation

up-regulates quantity by expression

0.474

Thus, these data suggest that the expression of Brn3b can be activated directly by Math5 and that it is also subject to positive feedback regulation by Brn3 proteins.

SIGNOR-261567

Q9H8V3

P41743

0

phosphorylation

up-regulates

0.474

Our data support a model in which pkc?-Mediated phosphorylation regulates ect2 binding to the oncogenic pkc?-Par6 complex thereby activating rac1 activity and driving transformed growth and invasion.

SIGNOR-170790

P50148

P30968

0

binding

up-regulates activity

0.474

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-257265

P50148

Q92847

0

binding

up-regulates activity

0.474

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-257380

P04234

Q9UKV5

0

polyubiquitination

down-regulates quantity by destabilization

0.474

Gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate.

SIGNOR-272670

P49795

P28482

0

phosphorylation

up-regulates

0.474

Phosphorylation of gaip by erk2 were abrogated when serine at position 151 in the rgs domain was substituted by an alanine residue using site-directed mutagenesis. Furthermore, the lysosomal-autophagic pathway was not stimulated in s151a-gaip mutant-expressing cells when compared with wild-type gaip-expressing cells. These results demonstrate that the gtpase-activating protein activity of gaip is stimulated by erk2 phosphorylation.

SIGNOR-129883

O14920

O15530

0

phosphorylation

up-regulates activity

0.474

We found that PDK1 directly phosphorylates IKKbeta at the Ser(181) residue in the activation loop, leading to NF-kappaB nuclear translocation and NF-kappaB-dependent anti-apoptotic gene expression.

SIGNOR-279088

Q9H1E3

P06493

0

phosphorylation

down-regulates activity

0.474

putative phosphorylation site for Cdk1 is present in the DNA-binding domain peptide. This site, corresponding to Ser 181 in the NUCKS primary structure, is phosphorylated in vitro by Cdk1 with a Km of approximately 35 μM [7]. Phosphorylation of Ser 181 in the synthetic, DNA-binding domain peptide reduces its affinity for DNA-by 100%.

SIGNOR-261959

P42338

P46109

0

binding

up-regulates activity

0.474

Here, we identify CRKL as a member of the class of PI3Kβ-interacting proteins. Silencing CRKL expression in PTEN-null human cancer cells leads to a decrease in p110β-dependent PI3K signaling and cell proliferation.In conclusion, our study identified CRKL as an important regulator of PI3K activity in PTEN-deficient tumor cells through its association with p110β/p85.

SIGNOR-255821

P36956

P49336

0

phosphorylation

up-regulates activity

0.474

Biochemical analyses reveal that SREBP-1c can be directly phosphorylated by CDK8 at the conserved Threonine-402 residue (T402) in vitro and in cultured mammalian cells ( xref ).|Therefore, the mechanism of CDK8 regulating SREBP functions is primarily through the phosphorylation initiated control of nuclear SREBP-1 protein stability.

SIGNOR-279688

P60568

Q9UL17

0

transcriptional regulation

down-regulates quantity by repression

0.473

T-bet Transactivates the IFNγ Gene and Represses the IL-2 Gene in EL4 Cells

SIGNOR-266233

O14757

O15297

0

dephosphorylation

down-regulates activity

0.473

Here we show that the oncogenic p53-induced serine/threonine phosphatase, PPM1D (or Wip1), dephosphorylates two ATM/ATR targets, Chk1 and p53. PPM1D binds Chk1 and dephosphorylates the ATR-targeted phospho-Ser 345, leading to decreased Chk1 kinase activity.

SIGNOR-248317

P05106

O15530

0

phosphorylation

down-regulates activity

0.473

PDK1 specifically phosphorylates Thr-753 in 3. Our data argue that phosphorylation of Thr-753, which is conserved in many subunits, reduces the ability of PTB-containing proteins to bind the NXX(pY) motif in 3.

SIGNOR-250266

Q9HCU9

P68400

0

phosphorylation

down-regulates quantity by destabilization

0.473

We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α') phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ε-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation.

SIGNOR-266407

P38398

P42574

0

cleavage

down-regulates quantity by destabilization

0.473

We demonstrate the cleavage and the consequential downregulation of full-length BRCA1 by caspase-3 during UV-induced apoptosis. Finally, mutation of a caspase-3 specific cleavage site (D/A1154) rendered BRCA1 non-cleavable.

SIGNOR-256326

O14641

Q9Y2G4

0

binding

up-regulates

0.473

Our data thus demonstrate that diversin and dishevelled function together in a mutually dependent fashion in zebrafish gastrulation and organ formation

SIGNOR-162142

Q9BQE3

Q8NG68

0

tyrosination

down-regulates

0.473

Tubulin tyrosine ligase (ttl) adds a c-terminal tyr to __tubulin as part of a tyrosination/detyrosination cycle present in most eukaryotic cells. / ttl inhibits spontaneous tubulin polymerization

SIGNOR-176918

Q12972

P19784

0

phosphorylation

up-regulates activity

0.473

Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2.

SIGNOR-251023

Q8NFZ4

Q9NQX3

0

binding

up-regulates activity

0.473

Gephyrin is believed to act as a scaffold at inhibitory synapses, in a manner analogous to that of the prototypic excitatory synaptic scaffold, PSD-95. The best-known function of gephyrin is to bring the inhibitory synaptic receptors and to stabilize them at the inhibitory synapses. gephyrin interacts with NL-2 and collybistin, suggesting that it may be critical for the maturation or maintenance of inhibitory synapses.

SIGNOR-264974

P15311

O94804

0

phosphorylation

up-regulates activity

0.473

Ezrin activation by LOK phosphorylation involves a PIP 2 -dependent wedge mechanism.|The specificity of kinases depends on local peptide consensus sequences, which in the case of ezrin phosphorylation by LOK involves the hydrophobic residue Y565 positioned -2 residues from T567.

SIGNOR-278204

P78352

Q06787

0

post transcriptional regulation

up-regulates quantity

0.473

These results point toward a novel mechanism by which FUS targets neuronal mRNA and given that these PSD-95 and Shank1 3'-UTR G quadruplex structures are also targeted by the fragile X mental retardation protein (FMRP), they raise the possibility that FUS and FMRP might work together to regulate the translation of these neuronal mRNA targets.

SIGNOR-262108

Q12904

P45983

0

phosphorylation

down-regulates

0.473

We further demonstrated that serine-140 residue of aimp1 was phosphorylated by jnk and alanine mutation of serine-140 suppressed lps-induced cell surface altogether, these results suggest that aimp1 is phosphorylated by jnk through tlr-myd88 pathway and lose the regulatory activity for er retention of gp96expression of gp96.

SIGNOR-165763

O75525

Q8IUQ4

0

polyubiquitination

down-regulates quantity by destabilization

0.473

We found that SIAH1 bound to an octapeptide sequence in T-STAR targeting it for proteasome-dependent degradation.

SIGNOR-272671

P45984

P52564

0

phosphorylation

up-regulates

0.473

A map kinase kinase kinase (mapkkk), termed ask1, was identified that activated two different subs of map kinase kinases (mapkk), sek1 (or mkk4) and mkk3/mapkk6 (or mkk6), which in turn activated stress-activated protein kinase (sapk, also known as jnk;c-jun amino-terminal kinase)

SIGNOR-45369

P10415

O00198

0

binding

down-regulates

0.472

Hrk, physically interacts with the death-repressor proteins bcl2 and bcl2l1. Hrk activates cell death at least in part by interacting with and inhibiting the protection afforded by bcl2 and bcl2l1.

SIGNOR-47794

O60674

P08575

0

dephosphorylation

down-regulates activity

0.472

Src homology-2 (SH2) containing tyrosine phosphatase and CD45 tyrosine phosphatase play a major role in modulating JAK-STAT pathway. SH2 containing tyrosine phosphatases include SHP1 and SHP2 (shatterproof 1 & 2). Their SH2 domains allow attachment to the phospho-tyrosine residues present on activated receptors, JAKs or STAT proteins, leading to dephosphorylation of the substrates.

SIGNOR-255679

P50148

P28336

0

binding

up-regulates

0.472

G-proteins of the q family have been implicated as mediators of bombesin receptors action. This suggests that nmb-r couples to g?q, and that grp-r and nmb-r show distinct g-protein coupling preferences in the xenopus oocyte.

SIGNOR-35864

Q9NYV6

P45984

0

phosphorylation

down-regulates

0.472

Inactivation is due to phosphorylation of tif-ia by c-jun n-terminal kinase (jnk) at a single threonine residue (thr 200). Phosphorylation at thr 200 impairs the interaction of tif-ia with pol i and the tbp-containing factor tif-ib/sl1, thereby abrogating initiation complex formation.

SIGNOR-134878

P63096

P47211

0

binding

up-regulates activity

0.472

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-256687

Q99962

Q5S007

0

phosphorylation

down-regulates

0.472

We show that lrrk2 affects synaptic endocytosis by phosphorylating endophilin-a1 at s75.

SIGNOR-192072

Q9UPY8

Q96GD4

0

phosphorylation

up-regulates

0.472

Phosphorylation of eb3 at s176 by aurora b ensures successful cytokinesis completion by promoting midbody mt stability and midbody stabilization.

SIGNOR-202130

P78352

Q5JU85

0

relocalization

up-regulates activity

0.472

Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1.IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.

SIGNOR-264907

Q9Y4K3

Q86UT6

0

binding

down-regulates activity

0.472

Immunoprecipitation experiments showed that NLRX1 interacted with TRAF6 and TRAF3, but not with TRAF2 or TRAF5. These results further suggest that NLRX1 specifically inhibits TLR-induced TRAF6-dependent NF-kB signaling through targeting TRAF6.

SIGNOR-260364

P49675

Q13285

0

transcriptional regulation

up-regulates quantity by expression

0.472

The in vivo existence of an SF-1 corepressor complex consisting of DAX-1, RNF31, and SMRT at the steroidogenic promoters of the human StAR and CYP19 genes. We demonstrate that RNF31 is necessary for the stable association of the DAX-1 corepressor complex with chromatin-bound SF-1, thereby inhibiting the recruitment of coactivators and Pol II and controlling basal transcription levels of SF-1 target genes.

SIGNOR-271788

O75886

P18031

0

dephosphorylation

up-regulates quantity by stabilization

0.472

Together, the results presented here demonstrate that PTP1B can influence RTK signaling in a previously unrecognized manner. We show that PTP1B directly targets STAM2, part of the ESCRT-0 endosomal sorting complex, and we provide the first evidence that tyrosine phosphorylation affects STAM localization and function. This regulatory mechanism could impact signaling downstream of numerous cell surface receptors that are ubiquitinated and recognized by this conserved sorting machinery.

SIGNOR-248406

P05305

P23946

0

cleavage

up-regulates activity

0.472

Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products.

SIGNOR-256356

Q13501

Q14596

0

binding

up-regulates

0.472

Nbr1 and p62 interact and form oligomers.

SIGNOR-184273

Q12959

P11171

0

relocalization

up-regulates activity

0.472

Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R.

SIGNOR-266011

P08514

Q99828

0

binding

up-regulates activity

0.472

The small GTPase Rac3 interacts with the integrin-binding protein CIB and promotes integrin alpha(IIb)beta(3)-mediated adhesion and spreading

SIGNOR-269061

Q92934

Q08209

0

dephosphorylation

up-regulates activity

0.471

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD|Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis.

SIGNOR-248694

P35222

P19784

0

phosphorylation

up-regulates quantity by stabilization

0.471

We show that CKII phosphorylates the N-terminal region of beta-catenin and we identified Ser29, Thr102, and Thr112 as substrates for the enzyme. We provide evidence that CKII regulates the cytoplasmic stability of beta-catenin and acts synergistically with GSK-3beta in the multi-protein complex that controls the degradation of beta-catenin.

SIGNOR-275993

P04629

P51149

0

binding

down-regulates activity

0.471

Endogenous TrkA and Rab7 form a complex. Inhibition of Rab7 potentiates the signaling of TrkA in response to brief stimulations with NGF

SIGNOR-261305

Q9C0C7

P42345

0

phosphorylation

down-regulates activity

0.471

We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.|mTOR phosphorylates AMBRA1 at Ser 52, inhibiting its role in ULK1 modification

SIGNOR-272986

Q13753

P08253

0

cleavage

up-regulates activity

0.471

Induction of Cell Migration by Matrix Metalloprotease-2 Cleavage of Laminin-5|MMP2 cleaved the Ln-5 gamma2 subunit at residue 587, exposing a putative cryptic promigratory site on Ln-5 that triggers cell motility. This altered form of Ln-5 is found in tumors and in tissues undergoing remodeling, but not in quiescent tissues. Cleavage of Ln-5 by MMP2 and the resulting activation of the Ln-5 cryptic site may provide new targets for modulation of tumor cell invasion and tissue remodeling.

SIGNOR-253240

Q12972

P68400

0

phosphorylation

up-regulates activity

0.471

Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2.

SIGNOR-250931

Q16819

Q99626

0

transcriptional regulation

up-regulates quantity by expression

0.471

TNF-α-induced down-regulation of CDX2 suppresses MEP1A expression in colitis|

SIGNOR-253965

P13569

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.471

Here we show that CHIP functions with Hsc70 to sense the folded state of CFTR and targets aberrant forms for proteasomal degradation by promoting their ubiquitination.

SIGNOR-272584

Q92847

O00230

0

binding

up-regulates

0.471

In human tissues cst-14 as well as cst-17 but not ss-14 bind the gh secretagogue receptor (ghs-r).

SIGNOR-91134

P50148

P30989

0

binding

up-regulates activity

0.471

Altogether, these results reveal for the first time the ability of hNTS1 to directly activate the Gαq-, Gαi1-, GαoA-, and Gα13-mediated signaling pathways

SIGNOR-278058

Q6NUQ1

Q92878

0

binding

up-regulates activity

0.471

We propose that p130, forming a complex with Rad50 through RINT-1, blocks telomerase-independent telomere lengthening in normal cells.

SIGNOR-265030

P28069

P78337

0

binding

up-regulates activity

0.471

A novel OTX-related homeodomain transcription factor has been identified on the basis of its ability to interact with the transactivation domain of the pituitary-specific POU domain protein, Pit-1. P-OTX is able to independently activate and to synergize with Pit-1 on pituitary-specific target gene promoters.

SIGNOR-219740

P23560

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.471

We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene.

SIGNOR-264540

P29475

Q9UQM7

0

phosphorylation

down-regulates activity

0.471

It was found that purified recombinant nNOS was phosphorylated by CaM-K Ialpha, CaM-K IIalpha, and CaM-K IV at Ser847 in vitro. Replacement of Ser847 with Ala (S847A) prevented phosphorylation by CaM kinases. Phosphorylated recombinant wild-type nNOS at Ser847 (approximately 0.5 mol of phosphate incorporation into nNOS) exhibited a 30% decrease of Vmax with little change of both the Km for L-arginine and Kact for CaM relative to unphosphorylated enzyme. The activity of mutant S847D was decreased to a level 50-60% as much as the wild-type enzyme. The decreased NOS enzyme activity of phosphorylated nNOS at Ser847 and mutant S847D was partially due to suppression of CaM binding, but not to impairment of dimer formation which is thought to be essential for enzyme activation.

SIGNOR-250635

O14965

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.471

Chfr, a mitotic stress checkpoint, plays an important role in cell cycle progression, tumor suppression and the processes that require the E3 ubiquitin ligase activity mediated by the RING finger domain. Chfr stimulates the formation of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome-dependent degradation of a number of cellular proteins including Plk1 and Aurora A.

SIGNOR-271463

P02647

Q8IZY2

0

binding

up-regulates activity

0.471

ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. HEK293 cells overexpressing ABCA7 showed specific binding and cross-linking of lipid-poor apoA-I. ABCA7 expression increased cellular phosphatidylcholine and sphingomyelin efflux to apoA-I in a manner similar to ABCA1 but had no effect on cholesterol efflux.

SIGNOR-265178

P63096

P49286

0

binding

up-regulates activity

0.471

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-256707

P05106

Q03405

0

binding

up-regulates activity

0.471

Recent evidence suggests that the activation of b3 integrin in podocytes mediates uPAR-induced cellular events leading to proteinuria

SIGNOR-253333

O95837

P25101

0

binding

up-regulates activity

0.471

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-257427

Q06124

P48357

0

binding

up-regulates activity

0.471

Because the long leptin receptor lacking tyrosine 985 exhibits a significantly reduced ability to activate ERK phosphorylation, this residue is at least in part mediating stimulation of the ERK pathway by ObRb. This residue binds SHP-2 and is required for tyrosine phosphorylation of SHP-2

SIGNOR-263506

P20273

P15907

0

glycosylation

down-regulates activity

0.471

CD22-ligand interaction is regulated by the activity of a b-galactoside a2,6- sialyltransferase that can inactivate CD22-mediated binding by sialylating the CD22 receptor itself. These observations suggest that N-linked glycosylation sites on the CD22 molecule may play a role in the regulation of CD22-mediated adhesion.

SIGNOR-261741

O14579

Q96PM5

0

polyubiquitination

down-regulates quantity by destabilization

0.471

PIRH2 promotes the ubiquitylation of epsilon-COP in vitro and in vivo and consequently promotes the degradation of epsilon-COP.

SIGNOR-272630

P67809

P28482

0

phosphorylation

up-regulates activity

0.47

ERK2 may also directly phosphorylate YB-1 and therefore promotes its ability to transactivate target genes.

SIGNOR-279227

Q15645

Q15013

0

binding

up-regulates activity

0.47

We have indeed showed that TRIP13 action to disassemble the Cdc20–Mad2 complex requires the presence of p31comet (Fig. 3A). We furthermore found that the joint action of TRIP13 and p31comet is also required for the release of Mad2 from MCC, for the complete disassembly of MCC and for relieving APC/C from checkpoint inhibition (Figs. 3 and and4).4).

SIGNOR-265971

P02511

P04637

0

transcriptional regulation

up-regulates quantity by expression

0.47

Aberrant expression of CRYAB has been shown to be associated with several neurological diseases and malignant neoplasms. To identify transcriptional regulators of CRYAB expression, we examined its promoter for binding sites of transcription factors and identified four potential AP-2 binding sites in addition to a p53 binding site reported previously|Taken together, our results indicate that AP-2_ up-regulates the transcription of the CRYAB gene through stabilizing p53

SIGNOR-253638

Q03113

O95136

0

binding

up-regulates

0.47

Serum-borne lysophosphatidic acid (lpa) and sphingosine 1-phosphophate (s1p) act through g12/13-coupled receptors to inhibit the hippo pathway kinases lats1/2 thereby activating yap and taz transcription co-activators, which are oncoproteins repressed by lats1/2.

SIGNOR-198556

Q8NE35

O76050

0

ubiquitination

up-regulates activity

0.47

If Neurl1 interacts and modulates the activity of CPEB3 and increases the translation of GluA1 and GluA2 mRNAs, this effect would be blocked if we abolished the interaction between CPEB3 and Neurl1.|Neurl1 Interacts with and Ubiquitinates a Translational Regulator of GluA1 and GluA2 : the Cytoplasmic Polyadenylation Element Binding Protein 3.

SIGNOR-278588

P35712

Q9BS16

0

binding

up-regulates activity

0.47

Here we report the cloning of a novel cDNA, termed Solt, from a mouse testis cDNA library. Its gene product, Solt, interacts with the leucine zipper region of SoxLZ/Sox6. In transient transfection assays with SoxLZ/Sox6 containing the transactivation domain of herpes simplex virus VP16, the expression of a luciferase reporter gene under the control of a promoter containing a synthetic cis element that is bound by the HMG box of SoxLZ/Sox6 was poorly enhanced in the presence of Solt.

SIGNOR-221820

Q14194

P49841

0

phosphorylation

up-regulates

0.47

Using in vitro kinase assays and pharmacological inhibition of gsk3 as described above for crmp2 and crmp4, it was found that thr509 (and presumably ser518 and thr514) of human crmp1 is phosphorylated by gsk3, following priming of ser522 by cdk5

SIGNOR-145999

P60484

Q9BXM7

0

phosphorylation

down-regulates activity

0.47

PINK1 interacts with and phosphorylates PTEN at Serine179, resulting in the activation of AKT and the inhibition of PTEN nuclear import.

SIGNOR-277915

P63000

Q8WWN8

0

gtpase-activating protein

down-regulates activity

0.47

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-260456

P48506

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.47

In both models, the inducer-modified and Nrf2-bound Keap1 is inactivated and, consequently, newly synthesized Nrf2 proteins bypass Keap1 and translocate into the nucleus, bind to the ARE and drive the expression of Nrf2 target genes such as NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), glutamate-cysteine ligase (GCL) and glutathione S transferases (GSTs).

SIGNOR-256277

Q9NZQ7

Q9NX76

0

stabilization

up-regulates quantity by stabilization

0.47

Furthermore, the observations that (i) CMTM6 affects PD-L1 protein stability at late time points after biosynthesis; (ii) CMTM6, CMTM4 and PD-L1 interact, as shown by co-immunoprecipitation; and that (iii) CMTM6 is largely located at the cell surface, collectively suggest a model in which CMTM6 interacts with PD-L1 at the tumour cell surface and thereby protects it from degradation

SIGNOR-274980

P40763

Q9Y4K3

0

ubiquitination

down-regulates activity

0.47

TRAF6 Interacts with STAT3 and Mediates the Ubiquitination of STAT3.|TRAF6 Represses the Transcriptional Activity of STAT3.

SIGNOR-278618

O14974

O95835

0

phosphorylation

up-regulates activity

0.47

LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.

SIGNOR-278184

P03372

O15111

0

phosphorylation

up-regulates activity

0.47

These results demonstrated an estrogen-mediated increase in the phosphorylation of ER\u03b1 at serine residue 118 by IKK\u03b1 ( Figure 5 H, bottom).|Wt IKKalpha, but not the IKKalpha kinase mutant, increased both estrogen dependent and -independent ERalpha activation.

SIGNOR-279696

P10415

P67775

0

dephosphorylation

up-regulates activity

0.47

The phosphorylation of Bcl-2 resulted in a reduction in anti-apoptotic function, implying that dephosphorylation promoted the anti-apoptotic activity of Bcl-2 protein in human tumor cell lines. Thus, the present findings suggest that ERK and PP2A are physiological regulators of Bcl-2 phosphorylation, and these enzymes exert an influence on the anti-apoptotic function of Bcl-2.phosphorylation of Bcl2 at Ser70 is proposed to be a dynamic process regulated by the sequential action of an agonist-activated Bcl2 kinase and PP2A.

SIGNOR-248624

O15078

Q7Z7A1

0

binding

down-regulates activity

0.47

CEP290 cooperates with Rab8a to promote ciliogenesis and this function is antagonized by CP110. CP110 in this complex is to keep CEP290 inactive in growing cells until cells are ready to undergo ciliogenesis as they transit into the quiescent state

SIGNOR-252149

P35241

P61586

0

phosphorylation

up-regulates activity

0.47

Rev-erbα interacted with OPHN-1, promoted RhoA activity and phosphorylation of ERM. etection of phosphorylated ezrin (Thr567)/radixin (Thr564)/moesin (Thr558)(p-ERM) in Rev-erbαfl/flCre− and Rev-erbαfl/flPF4Cre+ platelets using phospho-specific antibodies.

SIGNOR-268430

P42356

Q14156

0

binding

up-regulates quantity

0.47

PI4KA is recruited to plasma membrane by the adapter protein EFR3, which has two isoforms, EFR3A and EFR3B

SIGNOR-269092

P63000

P63096

0

binding

up-regulates activity

0.47

These findings indicate that both G alpha(i) and G beta gamma stimulate Rac and Cdc42 pathways with lysophosphatidic acid-induced cell spreading on fibronectin

SIGNOR-256530

Q9UPT9

P06493

0

phosphorylation

up-regulates activity

0.47

On the other hand, CDK1 enhances USP22 activity to stabilize CCNB1 during the G2/M phase.|Phosphorylation of USP22 by CDK1 enhances its activity in deubiquitinating CCNB1.

SIGNOR-278241

O95837

P21731

0

binding

up-regulates activity

0.47

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-257023

P08754

P18089

0

binding

up-regulates activity

0.47

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-256857