GleghornLab/Signor_3class · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels int64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
Q96FI4	P45983	0	phosphorylation	up-regulates activity	0.2	These data confirm that NEIL1 can be phosphorylated by JNK1 in vitro at S207, S306, and S61.	SIGNOR-278315
P13569	Q99942	0	ubiquitination	down-regulates quantity by destabilization	0.665	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation.	SIGNOR-271494
P09619	P29353	1	phosphorylation	up-regulates	0.659	In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc.	SIGNOR-36906
P04792	Q9Y243	0	phosphorylation	down-regulates	0.286	First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.	SIGNOR-186780
O95202	Q9Y276	2	binding	up-regulates activity	0.464	LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex.	SIGNOR-262543
Q9NZC7	P12931	0	phosphorylation	up-regulates	0.48	The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.	SIGNOR-123819
P12931	P05107	1	phosphorylation	down-regulates activity	0.449	PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.	SIGNOR-254740
P20309	P50148	2	binding	up-regulates activity	0.579	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-257018
P01584	P14778	2	binding	up-regulates activity	0.906	Pro-IL-1beta, mIL-1beta and mIL-beta all bind to IL-1RI, which recruits the IL-1 receptor accessory protein (IL-1RAcP) as a co-receptor.	SIGNOR-249511
O96017	Q9UQ84	1	phosphorylation	down-regulates activity	0.565	Inhibition of Exo1 activity by the DDR kinase Rad53.\|Unlike Sae2/CtIP activation by CDK, Exo1 phosphorylation by Rad53 limits extended resection of ssDNA at uncapped telomeres and consequently minimizes further activation of the DDR.	SIGNOR-279028
O43353	Q8N2H9	0	ubiquitination	up-regulates activity	0.374	Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination	SIGNOR-280452
P16144	P42338	2	binding	up-regulates	0.2	Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation.	SIGNOR-54615
P03209	Q92985	1	transcriptional regulation	down-regulates quantity by repression	0.2	EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs.	SIGNOR-266645
P63092	P32239	2	binding	up-regulates activity	0.264	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-256765
Q9Y5G7	Q9Y5I2	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-265716
P19793	P55055	2	binding	up-regulates	0.694	We provide genetic and molecular evidence that cholesterol homeostasis in scs does not require pparalpha and beta, but depends upon the tif2 coactivator and rxrbeta/lxrbeta heterodimers, in which rxrbeta af-2 is transcriptionally active.	SIGNOR-123091
Q6XZF7	P60953	1	guanine nucleotide exchange factor	up-regulates activity	0.572	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-260547
Q9BY41	Q9UPR3	2	binding	up-regulates quantity by stabilization	0.642	Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation.	SIGNOR-272650
P18850	Q16539	0	phosphorylation	up-regulates activity	0.585	This observation not only confirms the specific role for IFN-γ-induced p38 MAPK-dependent phosphorylation of ATF6 at the T166 site but also indicates a connection between phosphorylation and proteolytic activation.	SIGNOR-276841
P45984	O95140	1	phosphorylation	down-regulates	0.351	Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process	SIGNOR-198054
P0DP25	Q8N5S9	2	binding	up-regulates	0.608	The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases	SIGNOR-266344
P11142	Q99942	2	binding	up-regulates activity	0.387	JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex	SIGNOR-271493
Q92918	Q16584	1	phosphorylation	up-regulates	0.574	Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.	SIGNOR-83415
Q7KZF4	Q12772	0	transcriptional regulation	up-regulates quantity by expression	0.342	These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.	SIGNOR-259136
Q14289	P12931	0	phosphorylation	up-regulates	0.624	These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity.	SIGNOR-133870
O75676	P18846	1	phosphorylation	up-regulates	0.615	Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1.	SIGNOR-116252
Q13153	P53350	1	phosphorylation	up-regulates	0.552	We show here that pak1 is required for cell proliferation, mitotic progression and plk1 activity in hela cells. phosphorylation of plk1 on ser 49 is important for metaphase-associated events.	SIGNOR-178353
Q96PU5	Q14524	1	ubiquitination	down-regulates quantity by destabilization	0.464	The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).	SIGNOR-253456
O75376	Q96EB6	0	null	up-regulates	0.621	In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.	SIGNOR-253505
Q8IYT8	Q8TDY2	1	phosphorylation	up-regulates activity	0.747	When mTOR is inhibited, ULK1 and ULK2 activate and phosphorylate ATG13 and FIP200.	SIGNOR-280159
Q9NQU5	P15976	1	phosphorylation	up-regulates activity	0.2	In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.\|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.	SIGNOR-278415
Q9UQB8	Q8N8S7	2	binding	up-regulates activity	0.569	We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia.	SIGNOR-268423
O00408	P17612	2	binding	down-regulates activity	0.368	We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.	SIGNOR-275730
P46531	P80370	2	binding	down-regulates activity	0.518	Moreover, the interaction of DLK1 with NOTCH1 caused an inhibition of basal NOTCH signaling in preadipocytes and mesenchymal multipotent cells. In this work, we demonstrate, for the first time, that DLK2 interacts with itself, with DLK1, and with the same NOTCH1 receptor region as DLK1 does. We demonstrate also that the interaction of DLK2 with NOTCH1 similarly results in an inhibition of NOTCH signaling in preadipocytes and Mouse Embryo fibloblasts.	SIGNOR-172830
Q03113	P41968	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 ≥ -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-257407
Q13257	O43683	0	relocalization	up-regulates activity	0.96	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252018
P42345	O00141	1	phosphorylation	up-regulates	0.849	Mtor phosphorylated sgk1, but not sgk1-s422a, in vitro. Sgk1 phosphorylated p27 in vitro. These data implicate sgk1 as an mtorc1 (mtor-raptor) substrate. mtor may promote g1 progression in part through sgk1 activation	SIGNOR-179113
P19022	Q4KMG0	2	binding	up-regulates	0.648	We report here that n-cadherin ligation activates p38alpha/beta in myoblasts in a cdo-, bnip-2-, and jlp-dependent manner	SIGNOR-163844
P49841	Q13469	1	phosphorylation	down-regulates	0.561	Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.	SIGNOR-179784
P67870	P06493	0	phosphorylation	up-regulates	0.459	In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells.	SIGNOR-29462
Q9GZT9	Q16665	1	hydroxylation	down-regulates quantity by destabilization	0.918	Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.\|Oxygen-dependent hydroxylation by the prolyl hydroxylase domain-2 (PHD2) protein marks HIF-1alpha for ubiquitination by the von Hippel Lindau (VHL) tumor suppressor protein, leading to proteasomal degradation	SIGNOR-261994
O75582	P27361	0	phosphorylation	up-regulates	0.585	In the present study, we show that, in addition to being phosphorylated on thr-581 and ser-360 by erk1/2 or p38, msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758.	SIGNOR-131379
Q9NYL2	P45985	1	phosphorylation	up-regulates activity	0.2	We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.	SIGNOR-243348
Q9UP38	Q92997	2	binding	up-regulates activity	0.657	Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.	SIGNOR-258953
Q9P2J3	P49716	2	binding	down-regulates quantity by destabilization	0.251	KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ.	SIGNOR-272459
P14373	O00750	1	ubiquitination	down-regulates	0.402	We now show that trim27 functions as an e3 ligase and mediates lysine 48 polyubiquitination of pi3kc2_, leading to a decrease in pi3k enzyme activity.	SIGNOR-177935
Q07889	P01112	1	guanine nucleotide exchange factor	up-regulates activity	0.892	The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.	SIGNOR-59472
P06493	P62136	1	phosphorylation	down-regulates activity	0.575	Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.	SIGNOR-151799
P51684	P14780	1	null	up-regulates activity	0.2	We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase.	SIGNOR-278042
P54646	Q00535	0	phosphorylation	down-regulates activity	0.216	In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.\|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site.	SIGNOR-280218
P12931	Q7L0Q8	1	phosphorylation	down-regulates activity	0.534	Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src. Phosphorylation at Y254 negatively regulates Wrch-1-mediated biological functions.Serum-stimulated tyrosine phosphorylation and relocalization of Wrch-1 decreases its activation of downstream effectors in a Y254-dependent manner.	SIGNOR-259814
P26232	P46937	2	binding	down-regulates	0.329	The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation.	SIGNOR-201245
Q9HAW4	O14757	2	binding	up-regulates	0.794	Binding of claspin to xchk1 is highly elevated in the presence of dna templates that trigger a checkpoint arrest of the cell cycle in xenopus egg extracts	SIGNOR-84474
P31749	P18031	2	phosphorylation	down-regulates activity	0.742	Phosphorylation of ptp1b at ser(50) by akt impairs its ability to dephosphorylate the insulin receptor.	SIGNOR-252542
O75197	Q9H1J5	2	binding	up-regulates	0.633	Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.	SIGNOR-131987
P09493	P42336	0	phosphorylation	up-regulates activity	0.2	Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization.	SIGNOR-263027
P50281	Q99558	0	phosphorylation	up-regulates activity	0.2	A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).\|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.	SIGNOR-279631
O14654	P78368	0	phosphorylation	down-regulates quantity by destabilization	0.2	IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).	SIGNOR-277615
P62807	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265377
Q9UI12	P36897	2	binding	up-regulates activity	0.2	ATP6V1H interacts with TGF-β receptor I and AP-2 complex to regulate the proliferation and differentiation of BMSCs.	SIGNOR-266886
P32927	P29350	0	dephosphorylation	down-regulates	0.522	However, inhibition of shp2 binding to betac, did not prevent tyrosine phosphorylation of shp2. Interestingly, this same phosphopeptide served as a substrate for the tyrosine phosphatase activity of both shp1 and shp2.	SIGNOR-114597
P06493	Q86WB0	1	phosphorylation	down-regulates	0.253	Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1	SIGNOR-154047
O95983	O14965	0	phosphorylation	up-regulates	0.286	These results suggest that the biochemical changes of mbd3 may be intimately related to the targeting of mbd3 to centrosomes. aurora-a phosphorylates mbd3	SIGNOR-93693
P61978	P45983	0	phosphorylation	up-regulates	0.372	The current studies demonstrate the identification of hnrnp-k as a jnk and erk substrate. The phosphoacceptor sites for jnk and erk on the k protein are different, and indeed, erk phosphorylation results in biological consequences different from those of phosphorylation by jnk (49). Whereas erk phosphorylation on aa 284 and 353 contributes to k protein nuclear export and concomitant inhibition of rna translation (49), phosphorylation by k protein on aa 216 and 353 increases the transcriptional effects of the k protein.	SIGNOR-105770
Q9UQB3	Q96RT1	2	binding	up-regulates activity	0.2	We characterized the interactions between the Erbin PDZ domain and both ARVCF and δ-catenin in vitro and in vivo. endogenous δ-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that δ-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex.	SIGNOR-252120
P06493	P10275	1	phosphorylation	up-regulates	0.53	At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1	SIGNOR-175692
P50148	Q96LB1	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-257385
Q13233	Q8IVH8	0	phosphorylation	up-regulates	0.453	With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation	SIGNOR-61814
Q07812	O60260	0	ubiquitination	down-regulates quantity by destabilization	0.2	The E3 ligase parkin, which is known to trigger mitochondria specific autophagy, ubiquitylates BAX K128 and targets the pro apoptotic BCL-2 protein for proteasomal degradation.	SIGNOR-278529
P33981	P00519	1	phosphorylation	down-regulates	0.279	Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.	SIGNOR-181064
P48729	Q969R2	1	phosphorylation	up-regulates activity	0.2	CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.\|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.	SIGNOR-264877
Q5JTC6	P49841	1	relocalization	up-regulates activity	0.419	Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.	SIGNOR-171892
P53350	Q14790	1	phosphorylation	down-regulates quantity by destabilization	0.371	By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis.	SIGNOR-272989
Q8N1E6	P01106	1	ubiquitination	down-regulates quantity by destabilization	0.349	In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.	SIGNOR-274125
Q16236	Q14145	0	ubiquitination	down-regulates quantity	0.813	Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation	SIGNOR-259335
P31751	Q09472	1	phosphorylation	up-regulates	0.327	We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity	SIGNOR-148987
P51948	P04637	1	ubiquitination	down-regulates quantity by destabilization	0.351	Collectively, these results indicate that MNAT1 increases p53 ubiquitination, thus promoting its proteasomal degradation.\|These suggest that MNAT1 decreases p53 expression by the proteasome.	SIGNOR-278831
P03372	O14965	0	phosphorylation	up-regulates activity	0.357	Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .\|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.	SIGNOR-278508
Q16539	Q06413	1	phosphorylation	up-regulates activity	0.696	We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation.	SIGNOR-47136
P00533	Q12913	0	dephosphorylation	up-regulates quantity by stabilization	0.49	We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex\|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173	SIGNOR-248697
O15130	Q9GZQ6	2	binding	up-regulates	0.747	Npff specifically bound to npff1 (k(d) = 1.13 nm) and npff2 (k(d) = 0.37 nm), and both receptors were activated by npff in a variety of heterologous expression systems	SIGNOR-82916
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
O14965	Q8TEP8	2	phosphorylation	up-regulates activity	0.796	Thus, following their sequential activation in Cep192 complexes, both AurA and Plx1 phosphorylate Cep192.\|We found that Cep192 1\u20131000 -wt promoted AurA and Plx1 activation and itself underwent phosphorylation irrespective of whether it was bound to the endogenous or recombinant Plx1 (i.e. whether Plx1 was docked onto T46 or not) (lanes 6 and 8).	SIGNOR-279797
P68400	Q9UNN5	1	phosphorylation	down-regulates activity	0.326	We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.\|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 \| it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.	SIGNOR-250864
P08238	Q75N03	2	binding	up-regulates quantity	0.2	By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity.	SIGNOR-271475
P68036	O60260	1	ubiquitination	up-regulates activity	0.2	Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).	SIGNOR-272734
P45983	Q01094	1	phosphorylation	down-regulates activity	0.277	JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1	SIGNOR-279218
P50148	P55085	2	binding	up-regulates activity	0.406	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-257300
Q13588	P29353	2	binding	up-regulates	0.506	T cell activation effects an increase in grap association with p36/38, shc, sos, and dynamin.	SIGNOR-45528
P17612	P27987	1	phosphorylation	down-regulates activity	0.351	Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328	SIGNOR-249995
O43561	P19174	2	binding	up-regulates activity	0.808	By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively.	SIGNOR-246060
Q93079	Q14493	0	translation regulation	up-regulates quantity by expression	0.2	Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA\|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.	SIGNOR-265391
Q9NQ66	Q92997	0	null	up-regulates activity	0.347	Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin	SIGNOR-258980
O95714	P23025	1	ubiquitination	down-regulates	0.385	Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation	SIGNOR-164595
Q9BSI4	P08047	0	transcriptional regulation	up-regulates quantity by expression	0.2	Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression.	SIGNOR-271698
O43164	P10644	1	polyubiquitination	down-regulates quantity by destabilization	0.379	Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits	SIGNOR-271855
P15941	P12931	0	phosphorylation	up-regulates	0.444	The c-src tyrosine kinase regulates signaling of the human df3/muc1 carcinoma-associated antigen with gsk3 beta and betBeta-catenin c-src phosphorylates the muc1 cytoplasmic domain at a yekv motif c-src-mediated phosphorylation of muc1 increases binding of muc1 and betBeta-catenin	SIGNOR-85938
P01106	P24941	0	phosphorylation	up-regulates quantity by stabilization	0.749	Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ].	SIGNOR-279808
P12830	P68400	0	phosphorylation	up-regulates activity	0.401	Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. \| Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. \| Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion.	SIGNOR-250840
Q75N03	P07355	1	ubiquitination	down-regulates quantity by destabilization	0.2	By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2.	SIGNOR-271473

Q96FI4

P45983

0

phosphorylation

up-regulates activity

0.2

These data confirm that NEIL1 can be phosphorylated by JNK1 in vitro at S207, S306, and S61.

SIGNOR-278315

P13569

Q99942

0

ubiquitination

down-regulates quantity by destabilization

0.665

JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation.

SIGNOR-271494

P09619

P29353

1

phosphorylation

up-regulates

0.659

In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc.

SIGNOR-36906

P04792

Q9Y243

0

phosphorylation

down-regulates

0.286

First, the akt1, akt2, and akt3 isoforms can bind directly to hsp27 and can be found in a complex with p38 mapk, mk2, and hsp27 [98_100]. Second, rane and colleagues showed that akt could phosphorylate hsp27 at ser-82, but not ser-15 or ser-78, in vitro, while co-expression of an active akt mutant and hsp27 in hek cells resulted in hsp27 phosphorylation at the same residue.

SIGNOR-186780

O95202

Q9Y276

2

binding

up-regulates activity

0.464

LETM1 was co-precipitated with BCS1L and formation of the LETM1 complex depended on BCS1L levels, suggesting that BCS1L stimulates the assembly of the LETM1 complex.

SIGNOR-262543

Q9NZC7

P12931

0

phosphorylation

up-regulates

0.48

The tyrosine kinase, src, phosphorylates wwox at tyrosine 33 in the first ww domain and enhances its binding to p73.

SIGNOR-123819

P12931

P05107

1

phosphorylation

down-regulates activity

0.449

PTKs of the JAK and SRC families have a regulatory role in LFA-1 affinity triggering, with JAKs showing a positive role (3), whereas SRCs possibly have a negative role.

SIGNOR-254740

P20309

P50148

2

binding

up-regulates activity

0.579

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-257018

P01584

P14778

2

binding

up-regulates activity

0.906

Pro-IL-1beta, mIL-1beta and mIL-beta all bind to IL-1RI, which recruits the IL-1 receptor accessory protein (IL-1RAcP) as a co-receptor.

SIGNOR-249511

O96017

Q9UQ84

1

phosphorylation

down-regulates activity

0.565

Inhibition of Exo1 activity by the DDR kinase Rad53.|Unlike Sae2/CtIP activation by CDK, Exo1 phosphorylation by Rad53 limits extended resection of ssDNA at uncapped telomeres and consequently minimizes further activation of the DDR.

SIGNOR-279028

O43353

Q8N2H9

0

ubiquitination

up-regulates activity

0.374

Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination

SIGNOR-280452

P16144

P42338

2

binding

up-regulates

0.2

Stable expression of alpha6beta4 increased carcinoma invasion in a pi3k-dependent manner, and transient expression of a constitutively active pi3k increased invasion in the absence of alpha6beta4. Ligation of alpha6beta4 stimulated significantly more pi3k activity than ligation of beta1 integrins, establishing specificity among integrins for pi3k activation.

SIGNOR-54615

P03209

Q92985

1

transcriptional regulation

down-regulates quantity by repression

0.2

EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs.

SIGNOR-266645

P63092

P32239

2

binding

up-regulates activity

0.264

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-256765

Q9Y5G7

Q9Y5I2

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-265716

P19793

P55055

2

binding

up-regulates

0.694

We provide genetic and molecular evidence that cholesterol homeostasis in scs does not require pparalpha and beta, but depends upon the tif2 coactivator and rxrbeta/lxrbeta heterodimers, in which rxrbeta af-2 is transcriptionally active.

SIGNOR-123091

Q6XZF7

P60953

1

guanine nucleotide exchange factor

up-regulates activity

0.572

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-260547

Q9BY41

Q9UPR3

2

binding

up-regulates quantity by stabilization

0.642

Here, we report that the human ortholog of the yeast ever-shorter telomeres 1B (EST1B) binds HDAC8. This interaction is regulated by protein kinase A-mediated HDAC8 phosphorylation and protects human EST1B (hEST1B) from ubiquitin-mediated degradation.

SIGNOR-272650

P18850

Q16539

0

phosphorylation

up-regulates activity

0.585

This observation not only confirms the specific role for IFN-γ-induced p38 MAPK-dependent phosphorylation of ATF6 at the T166 site but also indicates a connection between phosphorylation and proteolytic activation.

SIGNOR-276841

P45984

O95140

1

phosphorylation

down-regulates

0.351

Jnk phosphorylation of mitofusin 2 in response to cellular stress leads to recruitment of the ubiquitin ligase (e3) huwe1/mule/arf-bp1/hecth9/e3histone/lasu1 to mitofusin 2, with the bh3 domain of huwe1 implicated in this interaction. This results in ubiquitin-mediated proteasomal degradation of mitofusin 2these data establish that mfn2 is phosphorylated on ser27 in response to a variety of cellular stresses and implicate jnk in this process

SIGNOR-198054

P0DP25

Q8N5S9

2

binding

up-regulates

0.608

The binding of Ca2+/CaM to CaM-KK is absolutely required for its activation and efficient phosphorylation of target protein kinases

SIGNOR-266344

P11142

Q99942

2

binding

up-regulates activity

0.387

JB12 cooperates with cytosolic Hsc70 and the ubiquitin ligase RMA1 to target CFTR and CFTRΔF508 for degradation. JB12 drives Hsc70 to associate with CFTR and the RMA1 E3 complex

SIGNOR-271493

Q92918

Q16584

1

phosphorylation

up-regulates

0.574

Hpk1 also phosphorylated mlk-3 activation loop in vitro, and ser281 was found to be the major phosphorylation site, indicating that hpk1 also activates mlk-3 via phosphorylation of the kinase activation loop.

SIGNOR-83415

Q7KZF4

Q12772

0

transcriptional regulation

up-regulates quantity by expression

0.342

These findings reveal that SREBP-2 and SREBP-1 bind to specific sites in SND1 promoter and regulate SND1 transcription in opposite ways; it is induced by SREBP-2 activating conditions and repressed by SREBP-1 overexpression.

SIGNOR-259136

Q14289

P12931

0

phosphorylation

up-regulates

0.624

These data indicate that pyk2 activation via phosphorylation at tyr-402 requires ?V?3 Ligation and src activity.

SIGNOR-133870

O75676

P18846

1

phosphorylation

up-regulates

0.615

Msk1 and msk2 directly phosphorilate and activate transcription factors such as creb1, atf1.

SIGNOR-116252

Q13153

P53350

1

phosphorylation

up-regulates

0.552

We show here that pak1 is required for cell proliferation, mitotic progression and plk1 activity in hela cells. phosphorylation of plk1 on ser 49 is important for metaphase-associated events.

SIGNOR-178353

Q96PU5

Q14524

1

ubiquitination

down-regulates quantity by destabilization

0.464

The control of Nav density at the cell membrane is crucial to ensuring normal neuronal excitability. Navs are subject to posttranslational modifications that may influence their cell membrane availability. Ubiquitylation is a key process that orchestrates the internalization and subsequent degradation or recycling of Navs. This is accomplished by ubiquitin protein ligases, such as NEDD4-2 (neuronal precursor cell expressed developmentally downregulated-4 type 2).

SIGNOR-253456

O75376

Q96EB6

0

null

up-regulates

0.621

In differentiated adipocyte cell lines, SIRT1 inhibits adipogenesis and enhances fat mobilization through lipolysis by suppressing the activity of PPARγ. SIRT1 achieves this by promoting the assembly of a corepressor complex, involving NCoR1 and SMRT, on the promoters of PPARγ target genes to repress their transcription.

SIGNOR-253505

Q8IYT8

Q8TDY2

1

phosphorylation

up-regulates activity

0.747

When mTOR is inhibited, ULK1 and ULK2 activate and phosphorylate ATG13 and FIP200.

SIGNOR-280159

Q9NQU5

P15976

1

phosphorylation

up-regulates activity

0.2

In addition, PAK5 knockdown also markedly reduced the association of GATA1 with HDAC3/4.|PAK5 phosphorylates the transcription factor GATA1 mainly at Ser161 and Ser 187, phosphorylated GATA1 recruits more HDAC3/4 to the promoter of E-cadherin and consequently suppresses the transcription of E-cadherin gene and promotes the EMT of breast cancer cells.

SIGNOR-278415

Q9UQB8

Q8N8S7

2

binding

up-regulates activity

0.569

We conclude that the interaction of Cdc42 with the partial CRIB motif of IRSp53 relieves an intramolecular, autoinhibitory interaction with the N terminus, allowing the recruitment of Mena to the IRSp53 SH3 domain. This IRSp53:Mena complex initiates actin filament assembly into filopodia.

SIGNOR-268423

O00408

P17612

2

binding

down-regulates activity

0.368

We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.

SIGNOR-275730

P46531

P80370

2

binding

down-regulates activity

0.518

Moreover, the interaction of DLK1 with NOTCH1 caused an inhibition of basal NOTCH signaling in preadipocytes and mesenchymal multipotent cells. In this work, we demonstrate, for the first time, that DLK2 interacts with itself, with DLK1, and with the same NOTCH1 receptor region as DLK1 does. We demonstrate also that the interaction of DLK2 with NOTCH1 similarly results in an inhibition of NOTCH signaling in preadipocytes and Mouse Embryo fibloblasts.

SIGNOR-172830

Q03113

P41968

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 ≥ -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-257407

Q13257

O43683

0

relocalization

up-regulates activity

0.96

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252018

P42345

O00141

1

phosphorylation

up-regulates

0.849

Mtor phosphorylated sgk1, but not sgk1-s422a, in vitro. Sgk1 phosphorylated p27 in vitro. These data implicate sgk1 as an mtorc1 (mtor-raptor) substrate. mtor may promote g1 progression in part through sgk1 activation

SIGNOR-179113

P19022

Q4KMG0

2

binding

up-regulates

0.648

We report here that n-cadherin ligation activates p38alpha/beta in myoblasts in a cdo-, bnip-2-, and jlp-dependent manner

SIGNOR-163844

P49841

Q13469

1

phosphorylation

down-regulates

0.561

Gsk3 was previously shown to directly phosphorylate the n-terminal regulatory domain of nfatc1, thus antagonizing the action of calcineurin and inhibiting nuclear shuttling of nfat.

SIGNOR-179784

P67870

P06493

0

phosphorylation

up-regulates

0.459

In cells, the casein kinase ii beta-subunit is phosphorylated at an autophosphorylation site and at a site (ser-209) that is maximally phosphorylated in mitotic cells. These studies provide strong biochemical evidence that p34cdc2 is the enzyme that phosphorylates ser-209 on the beta-subunit of ckii in mitotic cells.

SIGNOR-29462

Q9GZT9

Q16665

1

hydroxylation

down-regulates quantity by destabilization

0.918

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of erythropoiesis. In this article, we report 3 novel mutations, P378S, A385T, and G206C, on the EGLN1 gene encoding the negative HIF-1α regulator prolyl hydroxylase domain-2 (PHD2) in 3 patients with isolated erythrocytosis. These mutations impair PHD2 protein stability and partially reduce PHD2 activity, leading to increased HIF-1α protein levels in cultured cells.|Oxygen-dependent hydroxylation by the prolyl hydroxylase domain-2 (PHD2) protein marks HIF-1alpha for ubiquitination by the von Hippel Lindau (VHL) tumor suppressor protein, leading to proteasomal degradation

SIGNOR-261994

O75582

P27361

0

phosphorylation

up-regulates

0.585

In the present study, we show that, in addition to being phosphorylated on thr-581 and ser-360 by erk1/2 or p38, msk1 can autophosphorylate on at least six sites: ser-212, ser-376, ser-381, ser-750, ser-752 and ser-758.

SIGNOR-131379

Q9NYL2

P45985

1

phosphorylation

up-regulates activity

0.2

We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling.

SIGNOR-243348

Q9UP38

Q92997

2

binding

up-regulates activity

0.657

Upon ligand binding, DVL proteins are recruited to Frizzled receptors at the plasma membrane and co-recruit cytoplasmic transducers, such as Axin, CK1 and GSK3 binding protein (GBP), presumably along with their partners, to promote ?-catenin-dependent signalling.

SIGNOR-258953

Q9P2J3

P49716

2

binding

down-regulates quantity by destabilization

0.251

KLHL9 mediates poly-ubiquitylation of C/EBPβ and C/EBPδ isoforms. We confirmed KLHL9 deletions in an independent cohort and showed that this protein is necessary for Cul3-ligase mediated ubiquitylation and proteasomal degradation of established MES-GBM MRs, C/EBPβ and C/EBPδ.

SIGNOR-272459

P14373

O00750

1

ubiquitination

down-regulates

0.402

We now show that trim27 functions as an e3 ligase and mediates lysine 48 polyubiquitination of pi3kc2_, leading to a decrease in pi3k enzyme activity.

SIGNOR-177935

Q07889

P01112

1

guanine nucleotide exchange factor

up-regulates activity

0.892

The enhancement of H-Ras GTP levels induced by oncogenic K-Ras was abrogated when the expression of endogenous Sos was suppressed, implicating Sos as an essential intermediate in the cross talk between oncogenic K-Ras and WT H-Ras.

SIGNOR-59472

P06493

P62136

1

phosphorylation

down-regulates activity

0.575

Both of these pp1 isoforms contain an arg-pro-ile/val-thr-pro-pro-arg sequence near the c terminus, a known site of phosphorylation by cdc/cdk kinases, and phosphorylation attenuates phosphatase activity.

SIGNOR-151799

P51684

P14780

1

null

up-regulates activity

0.2

We hypothesized that MIP-3alpha promotes pancreatic cancer invasion through the up-regulation of MMP-9, a Type 4 collagenase.

SIGNOR-278042

P54646

Q00535

0

phosphorylation

down-regulates activity

0.216

In vitro, the results show that murine wild-type AMPK-alpha2 was phosphorylated by Cdk5 at a (S/T) PX (K/H/R) phosphorylation consensus sequence, which was associated with decreased AMPK-alpha2 activity.|Inactivated AMPK-alpha2 promotes the progression of diabetic brain damage by Cdk5 phosphorylation at Thr485 site.

SIGNOR-280218

P12931

Q7L0Q8

1

phosphorylation

down-regulates activity

0.534

Regulation of the Rho family small GTPase Wrch-1/RhoU by C-terminal tyrosine phosphorylation requires Src. Phosphorylation at Y254 negatively regulates Wrch-1-mediated biological functions.Serum-stimulated tyrosine phosphorylation and relocalization of Wrch-1 decreases its activation of downstream effectors in a Y254-dependent manner.

SIGNOR-259814

P26232

P46937

2

binding

down-regulates

0.329

The trimeric complex of alfa-catenin, 14-3-3, and yap sequesters yap at ajs and prevents yap dephosphorylation/activation.

SIGNOR-201245

Q9HAW4

O14757

2

binding

up-regulates

0.794

Binding of claspin to xchk1 is highly elevated in the presence of dna templates that trigger a checkpoint arrest of the cell cycle in xenopus egg extracts

SIGNOR-84474

P31749

P18031

2

phosphorylation

down-regulates activity

0.742

Phosphorylation of ptp1b at ser(50) by akt impairs its ability to dephosphorylate the insulin receptor.

SIGNOR-252542

O75197

Q9H1J5

2

binding

up-regulates

0.633

Wnt proteins bind to the frizzled receptors and lrp5/6 co-receptors, and through stabilizing the critical mediator betBeta-catenin, initiate a complex signaling cascade that plays an important role in regulating cell proliferation and differentiation.

SIGNOR-131987

P09493

P42336

0

phosphorylation

up-regulates activity

0.2

Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phosphorylation activity, we identify the cytoskeletal protein non-muscle tropomyosin as a substrate of PI(3)K, which is phosphorylated in a wortmannin-sensitive manner on residue Ser 61. A constitutively dephosphorylated (S61A) tropomyosin mutant blocks agonist-dependent betaAR internalization, whereas a tropomyosin mutant that mimics constitutive phosphorylation (S61D) complements the PI(3)K mutant, with only lipid phosphorylation activity reversing the defective betaAR internalization.

SIGNOR-263027

P50281

Q99558

0

phosphorylation

up-regulates activity

0.2

A post-transcriptional process is indicated because we observed that NIK increases MT1-MMP phosphorylation and activity, but does not affect MT1-MMP mRNA expression (XREF_FIG and XREF_FIG).|NIK increases MT1-MMP pseudopodial localization and enzymatic activity.

SIGNOR-279631

O14654

P78368

0

phosphorylation

down-regulates quantity by destabilization

0.2

IRS4 was phosphorylated at Ser859 by CK1γ2 in vitro and in vivo, which promoted the polyubiquitination and degradation of IRS4 through the ubiquitin/lysosome pathway by the carboxyl terminus of Hsc70-interacting protein(CHIP).

SIGNOR-277615

P62807

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265377

Q9UI12

P36897

2

binding

up-regulates activity

0.2

ATP6V1H interacts with TGF-β receptor I and AP-2 complex to regulate the proliferation and differentiation of BMSCs.

SIGNOR-266886

P32927

P29350

0

dephosphorylation

down-regulates

0.522

However, inhibition of shp2 binding to betac, did not prevent tyrosine phosphorylation of shp2. Interestingly, this same phosphopeptide served as a substrate for the tyrosine phosphatase activity of both shp1 and shp2.

SIGNOR-114597

P06493

Q86WB0

1

phosphorylation

down-regulates

0.253

Moreover, we found cyclin b1/cdk1 to phosphorylate nipa at ser-395 in mitosis. Mutation of both ser-359 and ser-395 impaired effective inactivation of the scfnipa complex, resulting in reduced levels of mitotic cyclin b1

SIGNOR-154047

O95983

O14965

0

phosphorylation

up-regulates

0.286

These results suggest that the biochemical changes of mbd3 may be intimately related to the targeting of mbd3 to centrosomes. aurora-a phosphorylates mbd3

SIGNOR-93693

P61978

P45983

0

phosphorylation

up-regulates

0.372

The current studies demonstrate the identification of hnrnp-k as a jnk and erk substrate. The phosphoacceptor sites for jnk and erk on the k protein are different, and indeed, erk phosphorylation results in biological consequences different from those of phosphorylation by jnk (49). Whereas erk phosphorylation on aa 284 and 353 contributes to k protein nuclear export and concomitant inhibition of rna translation (49), phosphorylation by k protein on aa 216 and 353 increases the transcriptional effects of the k protein.

SIGNOR-105770

Q9UQB3

Q96RT1

2

binding

up-regulates activity

0.2

We characterized the interactions between the Erbin PDZ domain and both ARVCF and δ-catenin in vitro and in vivo. endogenous δ-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that δ-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex.

SIGNOR-252120

P06493

P10275

1

phosphorylation

up-regulates

0.53

At first, the data show that cdk5 enables phosphorylation of ar at ser-81 site through direct biochemical interaction and, therefore, results in the stabilization of ar proteins although ar was reported as substrates for cdk9 (5) as well as cdk1

SIGNOR-175692

P50148

Q96LB1

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-257385

Q13233

Q8IVH8

0

phosphorylation

up-regulates

0.453

With regard to at least mekk1, serine/threonine kinases such as nik,glkand hpk1 appear also to be important for regulation

SIGNOR-61814

Q07812

O60260

0

ubiquitination

down-regulates quantity by destabilization

0.2

The E3 ligase parkin, which is known to trigger mitochondria specific autophagy, ubiquitylates BAX K128 and targets the pro apoptotic BCL-2 protein for proteasomal degradation.

SIGNOR-278529

P33981

P00519

1

phosphorylation

down-regulates

0.279

Ttk phosphorylation of thr735 was associated with partial inhibition of nuclear targeting of c-abl.

SIGNOR-181064

P48729

Q969R2

1

phosphorylation

up-regulates activity

0.2

CK1a1, JNK1 and CDK1 had the highest site-specific activity for ORP4L, while CDK1, GSK3a, CK1a1 and GSK3b showed the highest specificity for the site when corrected for background activity with ORP4L-S4A. Because of the complexity of the serine/proline-rich site, we did not determine which serine(s) in ORP4L were phosphorylated by candidate kinases.|We conclude that phosphorylation of a unique serine/proline motif in the ORD induces a conformation change in ORP4L that enhances interaction with vimentin and cholesterol extraction from membranes.

SIGNOR-264877

Q5JTC6

P49841

1

relocalization

up-regulates activity

0.419

Amer1 binds ck1gamma, recruits axin and gsk3beta to the plasma membrane and promotes complex formation between axin and lrp6.

SIGNOR-171892

P53350

Q14790

1

phosphorylation

down-regulates quantity by destabilization

0.371

By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis.

SIGNOR-272989

Q8N1E6

P01106

1

ubiquitination

down-regulates quantity by destabilization

0.349

In this study, we demonstrate that the deubiquitinase USP13 stabilizes c-Myc by antagonizing FBXL14-mediated ubiquitination to maintain GSC self-renewal and tumorigenic potential. USP13 was preferentially expressed in GSCs, and its depletion potently inhibited GSC proliferation and tumor growth by promoting c-Myc ubiquitination and degradation.

SIGNOR-274125

Q16236

Q14145

0

ubiquitination

down-regulates quantity

0.813

Keap1 is a substrate receptor of a Cul3-RING ubiquitin ligase (CRL3) that, in physiological conditions, constitutively binds and targets Nrf2 for degradation

SIGNOR-259335

P31751

Q09472

1

phosphorylation

up-regulates

0.327

We find that suberoylanilide hydroxamic acid stimulates akt activity, which is required to phosphorylate p300 at ser(1834). Akt-mediated phosphorylation of p300 dramatically increases its acetyltransferase activity

SIGNOR-148987

P51948

P04637

1

ubiquitination

down-regulates quantity by destabilization

0.351

Collectively, these results indicate that MNAT1 increases p53 ubiquitination, thus promoting its proteasomal degradation.|These suggest that MNAT1 decreases p53 expression by the proteasome.

SIGNOR-278831

P03372

O14965

0

phosphorylation

up-regulates activity

0.357

Based on these findings, we conclude that ER\u03b1-Ser167 and -Ser305 are phosphorylated by Aurora-A in vitro and in vivo .|These data suggest that Aurora-A not only activates ER\u03b1 activity but also enhances E2 action and that Aurora-A-induced ER\u03b1 activation could not be inhibited by tamoxifen.

SIGNOR-278508

Q16539

Q06413

1

phosphorylation

up-regulates activity

0.696

We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation.

SIGNOR-47136

P00533

Q12913

0

dephosphorylation

up-regulates quantity by stabilization

0.49

We report the identification of PTPRK and PTPRJ (density-enhanced phosphatase-1 [DEP-1]) as EGFR-targeting phosphatases. DEP-1 is a tumor suppressor that dephosphorylates and thereby stabilizes EGFR by hampering its ability to associate with the CBL-GRB2 ubiquitin ligase complex|By employing commercially available antibodies, which are supposed to recognize specific tyrosine phosphorylation sites of EGFR, we found that depletion of endogenous DEP-1 nonselectively increased receptor phosphorylation, affecting all three sites we analyzed (tyrosines 1045, 1068, and 1173

SIGNOR-248697

O15130

Q9GZQ6

2

binding

up-regulates

0.747

Npff specifically bound to npff1 (k(d) = 1.13 nm) and npff2 (k(d) = 0.37 nm), and both receptors were activated by npff in a variety of heterologous expression systems

SIGNOR-82916

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

O14965

Q8TEP8

2

phosphorylation

up-regulates activity

0.796

Thus, following their sequential activation in Cep192 complexes, both AurA and Plx1 phosphorylate Cep192.|We found that Cep192 1\u20131000 -wt promoted AurA and Plx1 activation and itself underwent phosphorylation irrespective of whether it was bound to the endogenous or recombinant Plx1 (i.e. whether Plx1 was docked onto T46 or not) (lanes 6 and 8).

SIGNOR-279797

P68400

Q9UNN5

1

phosphorylation

down-regulates activity

0.326

We previously identified the Fas-associated factor FAF1 as an in vitro substrate of protein kinase CK2 and determined Ser289 and Ser291 as phosphorylation sites.|Therefore we assume that CK2‐mediated FAF1 phosphorylation influences the nuclear localization of FAF1 | it implies that the major function of FAF1 might not be in the cytoplasm as an interacting partner of Fas.

SIGNOR-250864

P08238

Q75N03

2

binding

up-regulates quantity

0.2

By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2. Hsp90 participates in the correct folding of its client proteins, allowing them to maintain their stability and activity.

SIGNOR-271475

P68036

O60260

1

ubiquitination

up-regulates activity

0.2

Only UbcH5 and Related Class I E2s Support Ubiquitination of S5a—UbcH5 belongs to the Class I family of E2s which contains a catalytic core (UBC domain) without a distinct Ub binding domain (38). To test whether other Class I E2s can also support ubiquitination of S5a, we assayed the ubiquitination of S5a with UbcH7 and the E3s, Nedd4, or Parkin. With either of these E3s, UbcH7 supported ubiquitination of S5a (Fig. 8, A and B). In addition, another Class I E2, Ubc4, a close homolog of UbcH5, supported ubiquitination of S5a by the APC, a multimeric Ring finger E3 responsible for cell cycle progression through mitosis (39) (Fig. 8C). Thus, multiple Class I E2s can support ubiquitination of S5a by various types of E3s (Table 1).

SIGNOR-272734

P45983

Q01094

1

phosphorylation

down-regulates activity

0.277

JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1

SIGNOR-279218

P50148

P55085

2

binding

up-regulates activity

0.406

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-257300

Q13588

P29353

2

binding

up-regulates

0.506

T cell activation effects an increase in grap association with p36/38, shc, sos, and dynamin.

SIGNOR-45528

P17612

P27987

1

phosphorylation

down-regulates activity

0.351

Two isoforms of the inositol 1,4,5-trisphosphate 3-kinase have been identified, the A form and the B form. phosphorylation of isoform A by the cyclic AMP-dependent protein kinase increased activity 1.5-fold, whereas phosphorylation of isoform B decreased activity by 45%. major phosphorylation sites in the protein are Ser119 for PKA. Ser119 in the A isoform is conserved in the B isoform as Ser328

SIGNOR-249995

O43561

P19174

2

binding

up-regulates activity

0.808

By substituting these tyrosine residues in LAT with phenylalanine and by utilizing phosphorylated peptides derived from these sites, we mapped the tyrosine residues in LAT required for the direct interaction and activation of Vav, p85/p110alpha and phospholipase Cgamma1 (PLCgamma1). Our results indicate that Tyr(226) and Tyr(191) are required for Vav binding, whereas Tyr(171) and Tyr(132) are necessary for association and activation of phosphoinositide 3-kinase activity and PLCgamma1 respectively.

SIGNOR-246060

Q93079

Q14493

0

translation regulation

up-regulates quantity by expression

0.2

Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.

SIGNOR-265391

Q9NQ66

Q92997

0

null

up-regulates activity

0.347

Dsh through PLC activates IP3, which leads to release of intracellular Ca2+, which in turn activates CamK11 and calcineurin

SIGNOR-258980

O95714

P23025

1

ubiquitination

down-regulates

0.385

Herc2 may ubiquitinate xpa and thus target it for proteolytic degradation

SIGNOR-164595

Q9BSI4

P08047

0

transcriptional regulation

up-regulates quantity by expression

0.2

Transfection of a plasmid carrying the Sp1 transcription factor into Sp-deficient SL2 cells strongly activated TIN2 promoter-driven luciferase reporter expression.

SIGNOR-271698

O43164

P10644

1

polyubiquitination

down-regulates quantity by destabilization

0.379

Praja2 controls the stability of PKA regulatory subunits. Praja2 ubiquitylates RIIα/β subunits. Subunits

SIGNOR-271855

P15941

P12931

0

phosphorylation

up-regulates

0.444

The c-src tyrosine kinase regulates signaling of the human df3/muc1 carcinoma-associated antigen with gsk3 beta and betBeta-catenin c-src phosphorylates the muc1 cytoplasmic domain at a yekv motif c-src-mediated phosphorylation of muc1 increases binding of muc1 and betBeta-catenin

SIGNOR-85938

P01106

P24941

0

phosphorylation

up-regulates quantity by stabilization

0.749

Cdk2 phosphorylates c-Myc at Ser62 to suppress its ubiquitination modification/degradation, resulting in enhanced stability of c-Myc [ xref ].

SIGNOR-279808

P12830

P68400

0

phosphorylation

up-regulates activity

0.401

Casein kinase II phosphorylation of E-cadherin increases E-cadherin/beta-catenin interaction and strengthens cell-cell adhesion. | Under these conditions, phosphorylation of the E-cadherin double mutant S853A/S855A was reduced by 25% as compared with wt E-cadherin. | Expression of the E-cadherin double mutant S853A/S855A in NIH3T3 cells expressing Wnt-1 reduces cell-cell adhesion.

SIGNOR-250840

Q75N03

P07355

1

ubiquitination

down-regulates quantity by destabilization

0.2

By immunoprecipitation, we present evidence that Hakai interacts with Hsp90 chaperone complex in several epithelial cells and demonstrate that is a novel Hsp90 client protein. Interestingly, by overexpressing and knocking-down experiments with Hakai, we identified Annexin A2 as a Hakai-regulated protein. Interestingly, geldanamycin-induced Hakai degradation is accompanied by an increased expression of E-cadherin and Annexin A2.

SIGNOR-271473