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
O00762	P10275	transcriptional regulation	up-regulates quantity by expression	0.397	The evolution of prostate cancer from an androgen-dependent state (ADPCa) to one that is androgen-independent (AIPCa) marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in AIPCa is poorly understood. We have defined the direct AR-dependent target genes in both AIPCa and ADPCa by generating AR-dependent gene expression profiles and AR cistromes. In contrast to ADPCa, AR selectively up-regulates M-phase cell cycle genes in AIPCa including UBE2C, a gene that inactivates the M-phase checkpoint.	SIGNOR-251543
P17544	O00268	binding	down-regulates activity	0.397	These results not only demonstrate an interaction between ATF7 and TAF4 but also indicate, as in the case of TAF12 (see Figure 3e), that no additional cellular component is required for this binding. They also suggest that TAF4 may interfere with the formation of ATF7TAF12 subcomplexes, thereby inhibiting ATF7-induced transactivation.	SIGNOR-225300
P38398	Q7Z6Z7	ubiquitination	down-regulates quantity by destabilization	0.397	Collectively, these data indicate that HUWE1 targets BRCA1, but not BARD1, for polyubiquitination and degradation.Because HUWE1 promotes BRCA1 ubiquitination and degradation, we wondered whether it might contribute to the reduced BRCA1 protein levels in sporadic breast cancer.	SIGNOR-278583
P03372	P51948	phosphorylation	up-regulates activity	0.397	Human Estrogen Receptor α Is Phosphorylated at Serine 118 In Vivo by Cdk7	SIGNOR-260837
Q8IXJ6	Q00535	phosphorylation	up-regulates activity	0.397	Cdk5 phosphorylation-induced SIRT2 nuclear translocation promotes the death of dopaminergic neurons in Parkinson's disease.\|Moreover, the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of SIRT2 at the Ser331 and Ser335 sites appears to be necessary for such nuclear translocation.	SIGNOR-279684
Q92793	O75177	relocalization	up-regulates	0.397	The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.	SIGNOR-129926
P84022	Q8N6I1	binding	down-regulates	0.397	In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.	SIGNOR-119171
P16615	Q9UQM7	phosphorylation	up-regulates activity	0.397	SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix.	SIGNOR-250616
Q00653	Q969H0	binding	down-regulates quantity by destabilization	0.396	Fbxw7α is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Using differential purifications and mass spectrometry, we identified p100, an inhibitor of NF-κB signalling, as an interactor of Fbxw7α. p100 is constitutively targeted in the nucleus for proteasomal degradation by Fbxw7α	SIGNOR-272907
Q9BQQ3	P42574	cleavage	up-regulates activity	0.396	In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein	SIGNOR-260613
O75581	P12931	phosphorylation	down-regulates activity	0.396	Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.\|Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation.	SIGNOR-279289
Q7LDG7	P28482	phosphorylation	down-regulates activity	0.396	ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.	SIGNOR-279537
Q02556	P10914	binding	up-regulates activity	0.396	We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.	SIGNOR-222841
P49418	Q13627	phosphorylation	down-regulates	0.396	Recent studies show that phosphorylation of amphiphysin1 prd by cdk5 inhibited the association of amphiphysin1 with ap-2 in synaptic vesicle endocytosis (7, 8) similar to that by mapk (present report). Cdk5 appears to phosphorylate amphiphysin1 at serines 261, 272, 276, and 285 and threonine 310, located in the prd	SIGNOR-126843
Q13485	Q9UNE7	polyubiquitination	down-regulates quantity by destabilization	0.396	We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.	SIGNOR-272947
Q01668	P17612	phosphorylation	up-regulates activity	0.396	We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.	SIGNOR-263109
O95475	Q04724	binding	up-regulates activity	0.396	Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation	SIGNOR-234592
P15514	P19544	transcriptional regulation	up-regulates quantity by expression	0.396	The Wilms Tumor Suppressor WT1 Encodes a Transcriptional Activator of amphiregulin	SIGNOR-251745
P33032	Q8TCY5	binding	down-regulates activity	0.396	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-252368
P53355	Q9Y2M5	binding	down-regulates quantity by destabilization	0.396	Here, we identify the BTB-Kelch protein KLHL20 as a negative regulator of DAPK. KLHL20 binds DAPK and Cullin 3 (Cul3) via its Kelch-repeat domain and BTB domain, respectively. The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.	SIGNOR-271960
P31269	Q15910	transcriptional regulation	down-regulates quantity by repression	0.396	These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.	SIGNOR-260068
Q07820	Q9Y4K3	ubiquitination	up-regulates activity	0.396	TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .\|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers.	SIGNOR-278726
P46531	Q13627	phosphorylation	down-regulates	0.396	Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch .	SIGNOR-185494
P09038	P09629	transcriptional regulation	up-regulates quantity by expression	0.396	Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter.	SIGNOR-261639
P01903	Q12986	transcriptional regulation	down-regulates quantity by repression	0.396	A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor	SIGNOR-266224
P10275	O15164	binding	up-regulates	0.396	We found that trim24/transcriptional intermediary factor 1alpha (tif1alpha), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with ar and enhances transcriptional activity of ar	SIGNOR-189113
Q92974	Q96SB3	binding	up-regulates activity	0.396	The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc	SIGNOR-269176
P20336	Q8WXG6	guanine nucleotide exchange factor	up-regulates activity	0.396	Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).	SIGNOR-265579
P04637	O95155	polyubiquitination	down-regulates quantity by destabilization	0.396	We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis.	SIGNOR-271907
P01111	Q7Z5G4	palmitoylation	up-regulates activity	0.396	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261354
P61586	Q13618	ubiquitination	down-regulates quantity by destabilization	0.396	BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.	SIGNOR-264238
Q96SB3	Q00535	phosphorylation	down-regulates quantity	0.396	CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).\|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association.	SIGNOR-279453
P42771	O14920	phosphorylation	down-regulates	0.396	Ikkbeta specifically binds to p16 and phosphorylates ser8 of p16 phosphorylation at ser8 of p16 brings about a significant loss of its cyclin-dependent kinase (cdk) 4-inhibitory activity	SIGNOR-163801
Q14739	P06493	phosphorylation	down-regulates	0.396	The binding of the nk fragment to chromatin pretreated with an s-phase extract was suppressed by incubation with an m-phase extract. Enzyme inhibitor experiments revealed that multiple kinases participate in the suppression. One of these kinases was shown to be cdc2 experiments involving a mutant nk fragment showed that the phosphorylation of serine 71 by cdc2 kinase is responsible for the suppression.	SIGNOR-121335
P41594	Q02156	phosphorylation	up-regulates activity	0.396	Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.	SIGNOR-249288
P49427	P68400	phosphorylation	down-regulates activity	0.395	The ubiquitin-conjugating enzyme, cdc34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(kip1), ikappabalpha, wee1, and myod. We show that mammalian cdc34 is a phosphoprotein that is phosphorylated in proliferating cells. Phosphorylation of cdc34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of cdc34 at ck2-targeted residues, ser-203, ser-222, ser-231, thr-233, and ser-236, abolishes the phosphorylation of cdc34 observed in vivo and markedly shifts nuclearly localized cdc34 to the cytoplasm.	SIGNOR-110399
Q96KB5	P12931	phosphorylation	up-regulates quantity by stabilization	0.395	Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon	SIGNOR-277217
P53671	Q5VT25	phosphorylation	up-regulates activity	0.395	These results indicate that mrckalpha phosphorylates and activates lim kinases downstream of cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of adf/cofilin.	SIGNOR-107584
Q9Y570	Q14012	phosphorylation	up-regulates activity	0.395	CaMKI Is the Upstream Kinase for Phosphorylation of PME-1/Ser15	SIGNOR-277827
P55210	P12931	phosphorylation	up-regulates activity	0.395	Src enhances caspase-7 activity in vitro and in cells.\|When all four sites were mutated to phenylalanine, the in vitro kinase assay results showed that phosphorylation of the Mut-caspase-7 protein by Src decreased dramatically compared with Wt-caspase-7, suggesting that these four sites, Tyr58, Tyr151, Tyr229 and Tyr230, are the most important sites of caspase-7 to be phosphorylated by Src (XREF_FIG).	SIGNOR-278455
P27361	P30304	dephosphorylation	down-regulates	0.395	We found that cdc25a physically interacted with and de-phosphorylated phospho-erk both in vitro and in cell culture.	SIGNOR-133392
P18887	P68400	phosphorylation	up-regulates	0.395	Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair	SIGNOR-165419
P62136	Q00535	phosphorylation	down-regulates activity	0.395	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. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.	SIGNOR-92269
P55085	P08246	cleavage	down-regulates activity	0.395	PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases \| The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II\|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.\|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3	SIGNOR-263588
Q99683	P04049	binding	down-regulates	0.395	Raf-1 interacts with the proapoptotic, stress-activated protein kinase ask1 (apoptosis signal-regulating kinase 1) in vitro and in vivo.	SIGNOR-109023
Q99683	Q13627	phosphorylation	up-regulates activity	0.395	Moreover, Dyrk1A appears to directly phosphorylate the C-terminal domain of ASK1.\|The current finding that Dyrk1A enhances the activities of ASK1 and JNK1, it could act as a pro-apoptotic player.	SIGNOR-279366
Q8N726	O15119	transcriptional regulation	down-regulates quantity by repression	0.395	TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS	SIGNOR-249603
Q92934	Q15418	phosphorylation	down-regulates activity	0.395	We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites.	SIGNOR-249045
O00329	Q15303	binding	up-regulates	0.395	Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.	SIGNOR-146885
Q9Y6Q9	O15111	phosphorylation	up-regulates	0.395	Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.	SIGNOR-196953
Q9UN36	O00141	phosphorylation	up-regulates	0.395	Sgk1 phosphorylated ndrg2 at thr330, ser332 and thr348 in vitro. for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, the phosphorylation of thr348 by sgk1 may prime for phosphorylation at ser344	SIGNOR-129676
Q9GZM8	P60510	dephosphorylation	down-regulates activity	0.395	Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation\|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.\|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219	SIGNOR-248550
O43318	P49593	dephosphorylation	down-regulates activity	0.395	However, our current work shows that POPX2 can downregulate TAK1 and affect the anti-apoptotic activities of TAK1, implying that silencing POPX2 could facilitate TAK1 activation and will lead to increased cell survival.\|We have also demonstrated that POPX2 can directly dephosphorylate TAK1 (XREF_FIG).	SIGNOR-277047
P07332	P15311	relocalization	up-regulates	0.395	The recruitment and the activation of fes to the cell-cell contacts in confluent cells depend on its interaction with ezrin.	SIGNOR-159496
Q8IXJ6	P24941	phosphorylation	down-regulates	0.395	We define ser-331 as the site phosphorylated by cyclin e-cdk2, cyclin a-cdk2, and p35-cdk5 both in vitro and in cells. Importantly, phosphorylation at ser-331 inhibits the catalytic activity of sirt2.	SIGNOR-177972
P17676	P24941	phosphorylation	up-regulates	0.395	Mass spectrometric analysis revealed that cdk2/cyclina phosphorylates c/ebpbeta on thr(188) and is required for phosphorylation (on ser(184) or thr(179)) of c/ebpbeta by gsk3beta and maintenance of dna binding activity.	SIGNOR-196372
P51397	P42345	phosphorylation	down-regulates activity	0.395	A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.	SIGNOR-259812
Q96EB6	Q13131	phosphorylation	down-regulates activity	0.395	Previous studies have reported that AMP-activated protein kinase phosphorylates and inactivates SIRT1, resulting in increased p53 acetylation in liver cancer [ xref , xref ].	SIGNOR-280076
Q9UPY3	Q06945	transcriptional regulation	up-regulates quantity	0.395	.... showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least twofold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown	SIGNOR-258987
P43354	P28482	phosphorylation	up-regulates	0.395	We have shown that erk2 is a kinase to phosphorylate nurr1 on multiple sites. S126 and t132, which are located near af1 core of nurr1, are dominant sites phosphorylated by erk2. reporter gene assays show that nurr1delta124-133/t185a, an erk2 phospho-site mutant form, could not further increase its transcriptional activity on th promoter, suggesting that nurr1 phosphorylation by erk2 may regulate its transcriptional activity on th promoter.	SIGNOR-157167
P04049	P30304	dephosphorylation	down-regulates	0.395	Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity	SIGNOR-32548
P09471	P18825	binding	up-regulates activity	0.395	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-256978
P24385	Q13627	phosphorylation	down-regulates	0.395	Dyrk1a controls the rate of cycd1 degradation by directly phosphorylating cycd1 at thr 286 and thereby regulates the fraction of cycling cells.	SIGNOR-202838
P55010	P68400	phosphorylation	up-regulates	0.394	We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.	SIGNOR-141159
O95471	P09758	binding	up-regulates quantity	0.394	In summary, our findings provide evidence that Trop-2 is phosphorylated at Ser-322 by PKCα/δ and that this phosphorylation enhances cell motility and decreases claudin-7 localization to cellular borders.	SIGNOR-273822
P18847	Q99612	transcriptional regulation	up-regulates quantity by expression	0.394	KLF6 binds directly to and activates the ATF3 promoter.	SIGNOR-266051
P14598	Q05513	phosphorylation	up-regulates	0.394	Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.	SIGNOR-89280
Q13485	O75925	sumoylation	up-regulates	0.394	These data demonstrate that pias1 protein positively modulates tgf-beta responses as a sumo e3 ligase for smad4	SIGNOR-123462
P98170	P49841	phosphorylation	up-regulates activity	0.394	We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.	SIGNOR-277390
Q8IX90	P06493	phosphorylation	up-regulates activity	0.394	Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].\|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.	SIGNOR-278376
P30291	Q9Y297	binding	down-regulates	0.394	Scfb-trcp continues to have a role in this phase, however, through its induced degradation of the cdk1 inhibitor, wee1.	SIGNOR-128439
P17480	P28482	phosphorylation	down-regulates	0.394	Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna	SIGNOR-112809
O15534	P78368	phosphorylation	down-regulates	0.394	Ck1_ and ck1_2 can promote proteasome-dependent per1 degradation in mammalian tissue culture cells, and their removal by rnai leads to an increased abundance of per1.	SIGNOR-137751
P09874	P00533	phosphorylation	up-regulates activity	0.394	EGFR and MET heterodimer interacts with and phosphorylates PARP1.	SIGNOR-279169
Q7Z6J0	P31749	phosphorylation	down-regulates	0.394	We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac, as does phosphomimetic s304d and s304e mutation of posh.	SIGNOR-252501
P48431	P24941	phosphorylation	up-regulates activity	0.394	Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.	SIGNOR-279448
Q15643	P61019	binding	up-regulates activity	0.394	Vesicle-associated Rab2 then mediates attachment to the Rab2 binding site within the central coiled-coil region of GMAP-210, bringing the vesicle into closer proximity to the target membrane. GMAP-210 function in vivo is dependent upon its ability to tether membranes, which is mediated exclusively by the amino-terminal ALPS motif. Binding to Rab2 is also important for GMAP-210 function, although it is dispensable for tethering per se.	SIGNOR-261300
O14645	Q92949	transcriptional regulation	up-regulates quantity by expression	0.394	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266933
Q15303	Q6UW88	binding	up-regulates	0.394	Areg (amphiregulin), btc (beta-cellulin), egf, epgn (epigen), ereg (epiregulin), hbegf, nrg1, nrg2, nrg3, nrg4 and tgfa (tgfalpha) constitute egf family ligands for erbb family receptors.	SIGNOR-147835
P08581	Q6ZN28	transcriptional regulation	up-regulates quantity by expression	0.394	Human colon carcinoma SW480 cells express virtually no MACC1. MACC1 cDNA transfection led not only to strong increases in MACC1 mRNA expression (Fig. 3a), but also to a 40-fold upregulation of the HGF receptor MET mRNA expression (Fig. 3b). This was confirmed on the protein level	SIGNOR-266058
P56945	Q15678	dephosphorylation	down-regulates	0.394	We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation	SIGNOR-197923
Q96R06	P53350	phosphorylation	up-regulates activity	0.394	Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.\|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.	SIGNOR-279423
P63092	Q00987	binding	down-regulates activity	0.394	Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content.	SIGNOR-278070
Q92686	P17252	phosphorylation	up-regulates activity	0.394	Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.	SIGNOR-248913
Q13547	Q96EP1	polyubiquitination	down-regulates quantity by destabilization	0.394	Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.	SIGNOR-271465
Q07954	P12931	phosphorylation	up-regulates activity	0.394	We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras	SIGNOR-101535
Q15438	P06241	phosphorylation	up-regulates activity	0.394	Fyn directly binds, phosphorylates, and activates cytohesin-1.	SIGNOR-280015
Q9H257	P40337	binding	down-regulates activity	0.393	We found that pVHL associates with the NF-kappaB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C terminus by CK2.	SIGNOR-257603
Q9BZL6	P17252	phosphorylation	up-regulates activity	0.393	Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.\|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead.	SIGNOR-275955
Q9H4A3	P31749	phosphorylation	up-regulates	0.393	Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.	SIGNOR-252481
O95967	P35555	binding	down-regulates activity	0.393	Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.	SIGNOR-251860
P23588	P31749	phosphorylation	up-regulates	0.393	Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.	SIGNOR-252520
P46527	Q15418	phosphorylation	up-regulates activity	0.393	As for other PI3K effectors, RSK1 phosphorylates p27 at T198.\|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.	SIGNOR-279653
Q99102	P42224	transcriptional regulation	up-regulates quantity by expression	0.393	Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.	SIGNOR-254099
Q13547	P17844	binding	up-regulates	0.393	Wt p68 co-immunoprecipitates efficiently with hdac1, the k53r p68 does not / sumoylation is important for the interaction of p68 with hdac1 and for transcriptional repression by p68	SIGNOR-153715
P29353	Q16832	binding	up-regulates	0.393	Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes.	SIGNOR-140724
Q9Y618	P51843	binding	up-regulates activity	0.393	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-271785
Q8WUM4	P12931	phosphorylation	down-regulates activity	0.393	Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2.	SIGNOR-263201
P00533	O14965	phosphorylation	up-regulates activity	0.393	Because AURKA associated with EGFR, we next investigated whether AURKA phosphorylates EGFR at Thr654 and Ser1046.\|Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells.	SIGNOR-279589
Q06413	Q92585	binding	up-regulates	0.393	Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).	SIGNOR-144913

O00762

P10275

0

transcriptional regulation

up-regulates quantity by expression

0.397

The evolution of prostate cancer from an androgen-dependent state (ADPCa) to one that is androgen-independent (AIPCa) marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in AIPCa is poorly understood. We have defined the direct AR-dependent target genes in both AIPCa and ADPCa by generating AR-dependent gene expression profiles and AR cistromes. In contrast to ADPCa, AR selectively up-regulates M-phase cell cycle genes in AIPCa including UBE2C, a gene that inactivates the M-phase checkpoint.

SIGNOR-251543

P17544

O00268

0

binding

down-regulates activity

0.397

These results not only demonstrate an interaction between ATF7 and TAF4 but also indicate, as in the case of TAF12 (see Figure 3e), that no additional cellular component is required for this binding. They also suggest that TAF4 may interfere with the formation of ATF7TAF12 subcomplexes, thereby inhibiting ATF7-induced transactivation.

SIGNOR-225300

P38398

Q7Z6Z7

0

ubiquitination

down-regulates quantity by destabilization

0.397

Collectively, these data indicate that HUWE1 targets BRCA1, but not BARD1, for polyubiquitination and degradation.Because HUWE1 promotes BRCA1 ubiquitination and degradation, we wondered whether it might contribute to the reduced BRCA1 protein levels in sporadic breast cancer.

SIGNOR-278583

P03372

P51948

0

phosphorylation

up-regulates activity

0.397

Human Estrogen Receptor α Is Phosphorylated at Serine 118 In Vivo by Cdk7

SIGNOR-260837

Q8IXJ6

Q00535

0

phosphorylation

up-regulates activity

0.397

Cdk5 phosphorylation-induced SIRT2 nuclear translocation promotes the death of dopaminergic neurons in Parkinson's disease.|Moreover, the cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of SIRT2 at the Ser331 and Ser335 sites appears to be necessary for such nuclear translocation.

SIGNOR-279684

Q92793

O75177

0

relocalization

up-regulates

0.397

The calcium-responsive transactivator recruits creb binding protein to nuclear bodies.

SIGNOR-129926

P84022

Q8N6I1

0

binding

down-regulates

0.397

In this study, we examined the effect of eid-2 on smad-mediated tgf- signaling. Here, we show that eid-2 inhibits tgf- /smad transcriptional responses. Eid-2 interacts constitutively with smad proteins, and most strongly with smad3.

SIGNOR-119171

P16615

Q9UQM7

0

phosphorylation

up-regulates activity

0.397

SERCA2 and SERCA2 mutants S38A, S167A, and S531A were expressed in HEK-293 cells and tested for phosphorylation with CaM kinase. Mutant S38A was not phosphorylated, while mutants S167A and S531A were phosphorylated, suggesting that Ser38 is the site of CaM kinase phosphorylation in SERCA2. This conclusion was supported by the observation that phosphorylation of SERCA2 and mutants S167A and S531A by CaM kinase increased the Vmax for Ca2+ transport, while the Vmax for Ca2+ transport by mutant S38A was unaffected by exposure to a phosphorylation reaction mix.

SIGNOR-250616

Q00653

Q969H0

0

binding

down-regulates quantity by destabilization

0.396

Fbxw7α is a member of the F-box family of proteins, which function as the substrate-targeting subunits of SCF (Skp1/Cul1/F-box protein) ubiquitin ligase complexes. Using differential purifications and mass spectrometry, we identified p100, an inhibitor of NF-κB signalling, as an interactor of Fbxw7α. p100 is constitutively targeted in the nucleus for proteasomal degradation by Fbxw7α

SIGNOR-272907

Q9BQQ3

P42574

0

cleavage

up-regulates activity

0.396

In contrast, Caspase‐3 cleavage of GRASP‐1 releases the C‐terminal fragment, which in turn activates JNK signaling by serving as a scaffold protein

SIGNOR-260613

O75581

P12931

0

phosphorylation

down-regulates activity

0.396

Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly.|Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation.

SIGNOR-279289

Q7LDG7

P28482

0

phosphorylation

down-regulates activity

0.396

ERK2 phosphorylates RasGRP2 at Ser394 located in the linker region implicated in its autoinhibition.

SIGNOR-279537

Q02556

P10914

0

binding

up-regulates activity

0.396

We found that tyrosine phosphorylated ICSBP activates CYBB and NCF2 transcription, during late myeloid differentiation, by interacting with PU.1, IRF1 and CBP.

SIGNOR-222841

P49418

Q13627

0

phosphorylation

down-regulates

0.396

Recent studies show that phosphorylation of amphiphysin1 prd by cdk5 inhibited the association of amphiphysin1 with ap-2 in synaptic vesicle endocytosis (7, 8) similar to that by mapk (present report). Cdk5 appears to phosphorylate amphiphysin1 at serines 261, 272, 276, and 285 and threonine 310, located in the prd

SIGNOR-126843

Q13485

Q9UNE7

0

polyubiquitination

down-regulates quantity by destabilization

0.396

We demonstrate that the coexpression of Smad1 and Smad4 with the CHIP protein results in the degradation of the Smad proteins through a ubiquitin-mediated process.

SIGNOR-272947

Q01668

P17612

0

phosphorylation

up-regulates activity

0.396

We recently demonstrated that PKA activation led to increased alpha(1D) Ca(2+) channel activity in tsA201 cells by phosphorylation of the channel protein. Western blotting showed that the N terminus and C terminus were phosphorylated. Serines 1743 and 1816, two PKA consensus sites, were phosphorylated by PKA and identified by mass spectrometry.

SIGNOR-263109

O95475

Q04724

0

binding

up-regulates activity

0.396

Biochemical and mutational analysis shows that the Six domain of both SIX3 and SIX6 strongly interact with the QD domain of TLE1 and AES. TLE1 over-expression induces an enlargement of the eye field and reinforcesSIX3/SIX6 capability of initiating retina formation

SIGNOR-234592

P15514

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.396

The Wilms Tumor Suppressor WT1 Encodes a Transcriptional Activator of amphiregulin

SIGNOR-251745

P33032

Q8TCY5

0

binding

down-regulates activity

0.396

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-252368

P53355

Q9Y2M5

0

binding

down-regulates quantity by destabilization

0.396

Here, we identify the BTB-Kelch protein KLHL20 as a negative regulator of DAPK. KLHL20 binds DAPK and Cullin 3 (Cul3) via its Kelch-repeat domain and BTB domain, respectively. The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.

SIGNOR-271960

P31269

Q15910

0

transcriptional regulation

down-regulates quantity by repression

0.396

These data support the proposed regulatory impact of particular PRC2-proteins in expression of HOXA9 and HOXA10 in NK/T-cells. In mammalian cells knockdown of PRC2 components EZH2 or PHF1 led to upregulated HOXA gene expression.

SIGNOR-260068

Q07820

Q9Y4K3

0

ubiquitination

up-regulates activity

0.396

TRAF6 likely directly ubiquitinates MCL-1 since purified TRAF6 promoted the ubiquitination of recombinant GST-MCL-1 and co-expression of Tax with TRAF6 further enhanced MCL-1 ubiquitination .|Therefore, TRAF6 mediated MCL-1 stabilization appears to be a common mechanism of cell survival usurped by both viral and non viral cancers.

SIGNOR-278726

P46531

Q13627

0

phosphorylation

down-regulates

0.396

Dyrk1a physically interacts with the nicd inducing its phosphorylation in the ankyrin domain, thereby attenuating notch .

SIGNOR-185494

P09038

P09629

0

transcriptional regulation

up-regulates quantity by expression

0.396

Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter.

SIGNOR-261639

P01903

Q12986

0

transcriptional regulation

down-regulates quantity by repression

0.396

A novel cysteine-rich sequence-specific DNA-binding protein interacts with the conserved X-box motif of the human major histocompatibility complex class II genes via a repeated Cys-His domain and functions as a transcriptional repressor

SIGNOR-266224

P10275

O15164

0

binding

up-regulates

0.396

We found that trim24/transcriptional intermediary factor 1alpha (tif1alpha), which is known as a ligand-dependent nuclear receptor co-regulator, interacts with ar and enhances transcriptional activity of ar

SIGNOR-189113

Q92974

Q96SB3

0

binding

up-regulates activity

0.396

The Rho Family GEF Lfc Interacts with Neurabin and Spinophilin. Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. The results obtained in the present study suggest a mechanism by which neurabin or spinophilin contributes to the organization of the F-actin cytoskeleton in dendritic spines, and in turn to the regulation of spine morphology, via the activity-dependent recruitment of the Rho-specific GEF Lfc

SIGNOR-269176

P20336

Q8WXG6

0

guanine nucleotide exchange factor

up-regulates activity

0.396

Rab3A, a member of the Rab3 small G protein family, regulates Ca(2+)-dependent exocytosis of neurotransmitter. The cyclical activation and inactivation of Rab3A are essential for the Rab3A action in exocytosis. GDP-Rab3A is activated to GTP-Rab3A by Rab3 GDP/GTP exchange protein (Rab3 GEP), and GTP-Rab3A is inactivated to GDP-Rab3A by Rab3 GTPase-activating protein (Rab3 GAP).

SIGNOR-265579

P04637

O95155

0

polyubiquitination

down-regulates quantity by destabilization

0.396

We show that ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase, physically interacts with p53 and Hdm2 (also known as Mdm2 in mice). UBE4B promotes p53 polyubiquitination and degradation and inhibits p53-dependent transactivation and apoptosis.

SIGNOR-271907

P01111

Q7Z5G4

0

palmitoylation

up-regulates activity

0.396

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261354

P61586

Q13618

0

ubiquitination

down-regulates quantity by destabilization

0.396

BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3. Our studies reveal a previously unknown mechanism for controlling RhoA degradation and regulating RhoA function in various biological contexts, which involves a Cul3/BACURD ubiquitin ligase complex.

SIGNOR-264238

Q96SB3

Q00535

0

phosphorylation

down-regulates quantity

0.396

CDK5 decreased the expression of both spinophilin (30%) and neurabin (64%).|This suggests that CDK5 phosphorylation of spinophilin at Ser17 is not responsible for the CDK5 dependent increase in the spinophilin and PP1 association.

SIGNOR-279453

P42771

O14920

0

phosphorylation

down-regulates

0.396

Ikkbeta specifically binds to p16 and phosphorylates ser8 of p16 phosphorylation at ser8 of p16 brings about a significant loss of its cyclin-dependent kinase (cdk) 4-inhibitory activity

SIGNOR-163801

Q14739

P06493

0

phosphorylation

down-regulates

0.396

The binding of the nk fragment to chromatin pretreated with an s-phase extract was suppressed by incubation with an m-phase extract. Enzyme inhibitor experiments revealed that multiple kinases participate in the suppression. One of these kinases was shown to be cdc2 experiments involving a mutant nk fragment showed that the phosphorylation of serine 71 by cdc2 kinase is responsible for the suppression.

SIGNOR-121335

P41594

Q02156

0

phosphorylation

up-regulates activity

0.396

Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.

SIGNOR-249288

P49427

P68400

0

phosphorylation

down-regulates activity

0.395

The ubiquitin-conjugating enzyme, cdc34, has been implicated in the ubiquitination of a number of vertebrate substrates, including p27(kip1), ikappabalpha, wee1, and myod. We show that mammalian cdc34 is a phosphoprotein that is phosphorylated in proliferating cells. Phosphorylation of cdc34 by the associated kinase maps predominantly to residues 203 and 222. Mutation of cdc34 at ck2-targeted residues, ser-203, ser-222, ser-231, thr-233, and ser-236, abolishes the phosphorylation of cdc34 observed in vivo and markedly shifts nuclearly localized cdc34 to the cytoplasm.

SIGNOR-110399

Q96KB5

P12931

0

phosphorylation

up-regulates quantity by stabilization

0.395

Phosphorylation of TOPK at Y74, Y272 by Src increases the stability of TOPK and promotes tumorigenesis of colon

SIGNOR-277217

P53671

Q5VT25

0

phosphorylation

up-regulates activity

0.395

These results indicate that mrckalpha phosphorylates and activates lim kinases downstream of cdc42, which in turn regulates the actin cytoskeletal reorganization through the phosphorylation and inactivation of adf/cofilin.

SIGNOR-107584

Q9Y570

Q14012

0

phosphorylation

up-regulates activity

0.395

CaMKI Is the Upstream Kinase for Phosphorylation of PME-1/Ser15

SIGNOR-277827

P55210

P12931

0

phosphorylation

up-regulates activity

0.395

Src enhances caspase-7 activity in vitro and in cells.|When all four sites were mutated to phenylalanine, the in vitro kinase assay results showed that phosphorylation of the Mut-caspase-7 protein by Src decreased dramatically compared with Wt-caspase-7, suggesting that these four sites, Tyr58, Tyr151, Tyr229 and Tyr230, are the most important sites of caspase-7 to be phosphorylated by Src (XREF_FIG).

SIGNOR-278455

P27361

P30304

0

dephosphorylation

down-regulates

0.395

We found that cdc25a physically interacted with and de-phosphorylated phospho-erk both in vitro and in cell culture.

SIGNOR-133392

P18887

P68400

0

phosphorylation

up-regulates

0.395

Xrcc1 phosphorylation by ck2 is required for its stability and efficient dna repair

SIGNOR-165419

P62136

Q00535

0

phosphorylation

down-regulates activity

0.395

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. Increasing doses of cdk2 resulted in increased phosphorylation of the thr-320 site. Phosphorylation of this site in pp1 corresponded to decreased pp1 activity.

SIGNOR-92269

P55085

P08246

0

cleavage

down-regulates activity

0.395

PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36-Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3

SIGNOR-263588

Q99683

P04049

0

binding

down-regulates

0.395

Raf-1 interacts with the proapoptotic, stress-activated protein kinase ask1 (apoptosis signal-regulating kinase 1) in vitro and in vivo.

SIGNOR-109023

Q99683

Q13627

0

phosphorylation

up-regulates activity

0.395

Moreover, Dyrk1A appears to directly phosphorylate the C-terminal domain of ASK1.|The current finding that Dyrk1A enhances the activities of ASK1 and JNK1, it could act as a pro-apoptotic player.

SIGNOR-279366

Q8N726

O15119

0

transcriptional regulation

down-regulates quantity by repression

0.395

TBX2 and TBX3 function as transcriptional repressors and both have been shown to inhibit myogenesis (Carlson et al, 2002; Zhu et al, 2014). Abnormal expression of TBX2 has been reported in several cancers including breast, pancreas, and melanoma, where it has been shown to drive proliferation (reviewed in Abrahams et al (2010)). As has been previously shown in other cell types, TBX2 was found to induce a downregulation of p14/19ARF and function as a direct repressor of p21 in RMS

SIGNOR-249603

Q92934

Q15418

0

phosphorylation

down-regulates activity

0.395

We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites.

SIGNOR-249045

O00329

Q15303

0

binding

up-regulates

0.395

Pi3k is the sole binding partner to six tyrosines of erbb3 and one in erbb4.

SIGNOR-146885

Q9Y6Q9

O15111

0

phosphorylation

up-regulates

0.395

Herein, we report the successful identification of six functional in vivo src-3 phosphorylation sites.

SIGNOR-196953

Q9UN36

O00141

0

phosphorylation

up-regulates

0.395

Sgk1 phosphorylated ndrg2 at thr330, ser332 and thr348 in vitro. for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, for example, the phosphorylation of thr330 or ser332 by sgk1 may prime ndrg2 for phosphorylation by gsk3 at ser326 and ser328 respectively, the phosphorylation of thr348 by sgk1 may prime for phosphorylation at ser344

SIGNOR-129676

Q9GZM8

P60510

0

dephosphorylation

down-regulates activity

0.395

Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule organization via NDEL1 dephosphorylation|PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.|We next examined the ability of PP4c to dephosphorylate a Cdk1 phosphorylation site, phospho-T219

SIGNOR-248550

O43318

P49593

0

dephosphorylation

down-regulates activity

0.395

However, our current work shows that POPX2 can downregulate TAK1 and affect the anti-apoptotic activities of TAK1, implying that silencing POPX2 could facilitate TAK1 activation and will lead to increased cell survival.|We have also demonstrated that POPX2 can directly dephosphorylate TAK1 (XREF_FIG).

SIGNOR-277047

P07332

P15311

0

relocalization

up-regulates

0.395

The recruitment and the activation of fes to the cell-cell contacts in confluent cells depend on its interaction with ezrin.

SIGNOR-159496

Q8IXJ6

P24941

0

phosphorylation

down-regulates

0.395

We define ser-331 as the site phosphorylated by cyclin e-cdk2, cyclin a-cdk2, and p35-cdk5 both in vitro and in cells. Importantly, phosphorylation at ser-331 inhibits the catalytic activity of sirt2.

SIGNOR-177972

P17676

P24941

0

phosphorylation

up-regulates

0.395

Mass spectrometric analysis revealed that cdk2/cyclina phosphorylates c/ebpbeta on thr(188) and is required for phosphorylation (on ser(184) or thr(179)) of c/ebpbeta by gsk3beta and maintenance of dna binding activity.

SIGNOR-196372

P51397

P42345

0

phosphorylation

down-regulates activity

0.395

A critical step in autophagy induction comprises the inactivation of a key negative regulator of the process, the Ser/Thr kinase mammalian target of rapamycin (mTOR). Here we identify death-associated protein 1 (DAP1) as a novel substrate of mTOR that negatively regulates autophagy. Mapping of the phosphorylation sites and analysis of phosphorylation mutants indicated that DAP1 is functionally silenced in growing cells through mTOR-dependent phosphorylations on Ser3 and Ser51.

SIGNOR-259812

Q96EB6

Q13131

0

phosphorylation

down-regulates activity

0.395

Previous studies have reported that AMP-activated protein kinase phosphorylates and inactivates SIRT1, resulting in increased p53 acetylation in liver cancer [ xref , xref ].

SIGNOR-280076

Q9UPY3

Q06945

0

transcriptional regulation

up-regulates quantity

0.395

.... showed that Sox4 positively regulates Dicer expression by binding to its promoter sequences and enhancing its activity. We found that knockdown of Dicer enhances the matrigel invasion of melanoma cells by at least twofold. In addition, we revealed that overexpression of exogenous Dicer reverts the enhanced melanoma cell invasion upon Sox4 knockdown

SIGNOR-258987

P43354

P28482

0

phosphorylation

up-regulates

0.395

We have shown that erk2 is a kinase to phosphorylate nurr1 on multiple sites. S126 and t132, which are located near af1 core of nurr1, are dominant sites phosphorylated by erk2. reporter gene assays show that nurr1delta124-133/t185a, an erk2 phospho-site mutant form, could not further increase its transcriptional activity on th promoter, suggesting that nurr1 phosphorylation by erk2 may regulate its transcriptional activity on th promoter.

SIGNOR-157167

P04049

P30304

0

dephosphorylation

down-regulates

0.395

Cdc25a can act on substrates other than cdks, since it dephosphorylates the homeodomain transcription factor cut and interacts with and dephosphorylates the proto-oncogene raf-1, resulting in a significant decrease in raf-1 kinase activity

SIGNOR-32548

P09471

P18825

0

binding

up-regulates activity

0.395

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-256978

P24385

Q13627

0

phosphorylation

down-regulates

0.395

Dyrk1a controls the rate of cycd1 degradation by directly phosphorylating cycd1 at thr 286 and thereby regulates the fraction of cycling cells.

SIGNOR-202838

P55010

P68400

0

phosphorylation

up-regulates

0.394

We find that eif5 is associated with ck2 when the kinase activity is at the highest level in vivo, and is phosphorylated at ser389 and ser390 by ck2.

SIGNOR-141159

O95471

P09758

0

binding

up-regulates quantity

0.394

In summary, our findings provide evidence that Trop-2 is phosphorylated at Ser-322 by PKCα/δ and that this phosphorylation enhances cell motility and decreases claudin-7 localization to cellular borders.

SIGNOR-273822

P18847

Q99612

0

transcriptional regulation

up-regulates quantity by expression

0.394

KLF6 binds directly to and activates the ATF3 promoter.

SIGNOR-266051

P14598

Q05513

0

phosphorylation

up-regulates

0.394

Phosphopeptide mapping of p47(phox) showed that, as opposed to pkc zeta, pkc alpha, beta ii, and delta are able to phosphorylate all the major pkc sites. The use of p47(phox) mutants identified serines 303, 304, 315, 320, 328, 359, 370, and 379 as targets of pkc alpha, beta ii, and delta.Taken together, these results suggest that pkc alpha, beta ii, delta, and zeta expressed in human neutrophils can individually phosphorylate p47(phox) and induce both its translocation and nadph oxidase activation.

SIGNOR-89280

Q13485

O75925

0

sumoylation

up-regulates

0.394

These data demonstrate that pias1 protein positively modulates tgf-beta responses as a sumo e3 ligase for smad4

SIGNOR-123462

P98170

P49841

0

phosphorylation

up-regulates activity

0.394

We now demonstrate that XIAP is phosphorylated by GSK3 at threonine 180, and that an alanine mutant (XIAPT180A) exhibits decreased Wnt activity compared to wild-type XIAP in cultured human cells and in Xenopus embryos.

SIGNOR-277390

Q8IX90

P06493

0

phosphorylation

up-regulates activity

0.394

Cdk1 treatment further enhanced the binding of Ska3 2D to Ndc80, suggesting that phosphorylation of other Cdk1 sites in Ska3 further contributes to the Ndc80C-Ska3 interaction, although this contribution is not apparent in our kinetochore localization assay.We next purified the GST-Ndc80C Bonsai construct that lacks the loop region of Ndc80 as well as the coiled coil regions of Ndc80C [17].|Thus, Ska3 can be phosphorylated by Cdk1 on T358 and T360 sites in vitro.We next tested whether Ska3 was required for Ska1 or Ska2 localization.

SIGNOR-278376

P30291

Q9Y297

0

binding

down-regulates

0.394

Scfb-trcp continues to have a role in this phase, however, through its induced degradation of the cdk1 inhibitor, wee1.

SIGNOR-128439

P17480

P28482

0

phosphorylation

down-regulates

0.394

Erk1/2 was found to phosphorylate the architectural transcription factor ubf at amino acids 117 and 201 within hmg boxes 1 and 2, preventing their interaction with dna

SIGNOR-112809

O15534

P78368

0

phosphorylation

down-regulates

0.394

Ck1_ and ck1_2 can promote proteasome-dependent per1 degradation in mammalian tissue culture cells, and their removal by rnai leads to an increased abundance of per1.

SIGNOR-137751

P09874

P00533

0

phosphorylation

up-regulates activity

0.394

EGFR and MET heterodimer interacts with and phosphorylates PARP1.

SIGNOR-279169

Q7Z6J0

P31749

0

phosphorylation

down-regulates

0.394

We report here that posh is a direct substrate for phosphorylation by akt in vivo and in vitro, and we identify a major site of akt phosphorylation as serine 304 of posh, which lies within the rac-binding domain. We further show that phosphorylation of posh results in a decreased ability to bind activated rac, as does phosphomimetic s304d and s304e mutation of posh.

SIGNOR-252501

P48431

P24941

0

phosphorylation

up-regulates activity

0.394

Cdk2 physically interacts with Sox2 and phosphorylates Sox2 at Ser 39 and Ser 253 in vitro.

SIGNOR-279448

Q15643

P61019

0

binding

up-regulates activity

0.394

Vesicle-associated Rab2 then mediates attachment to the Rab2 binding site within the central coiled-coil region of GMAP-210, bringing the vesicle into closer proximity to the target membrane. GMAP-210 function in vivo is dependent upon its ability to tether membranes, which is mediated exclusively by the amino-terminal ALPS motif. Binding to Rab2 is also important for GMAP-210 function, although it is dispensable for tethering per se.

SIGNOR-261300

O14645

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.394

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266933

Q15303

Q6UW88

0

binding

up-regulates

0.394

Areg (amphiregulin), btc (beta-cellulin), egf, epgn (epigen), ereg (epiregulin), hbegf, nrg1, nrg2, nrg3, nrg4 and tgfa (tgfalpha) constitute egf family ligands for erbb family receptors.

SIGNOR-147835

P08581

Q6ZN28

0

transcriptional regulation

up-regulates quantity by expression

0.394

Human colon carcinoma SW480 cells express virtually no MACC1. MACC1 cDNA transfection led not only to strong increases in MACC1 mRNA expression (Fig. 3a), but also to a 40-fold upregulation of the HGF receptor MET mRNA expression (Fig. 3b). This was confirmed on the protein level

SIGNOR-266058

P56945

Q15678

0

dephosphorylation

down-regulates

0.394

We show that p130 crk-associated substrate (p130cas) is a direct substrate of ptpn14 and that ptpn14 specifically regulates p130cas phosphorylation at tyrosine residue 128 (y128) in colorectal cancer (crc) cells. We engineered crc cells homozygous for a p130cas y128f knock-in mutant and found that these cells exhibit significantly reduced migration and colony formation

SIGNOR-197923

Q96R06

P53350

0

phosphorylation

up-regulates activity

0.394

Phosphorylation of the astrin N-terminal domain by Plk1 contributes to kinetochore\u2013microtubule attachment stability.|Taken together with the localisation data in XREF_FIG B, these data suggest that the presence of the Plk1 phosphorylated astrin N-terminus promotes the accumulation of the astrin complex at attached kinetochores, without which attachments appear more prone to dissociate.

SIGNOR-279423

P63092

Q00987

0

binding

down-regulates activity

0.394

Western blotting showed that increased MDM2 expression decreased Gαs protein content in HEK293 cells (Fig. 4B). Taken together, these data indicate that MDM2 binds to Gαs and has a direct impact on Gαs protein content.

SIGNOR-278070

Q92686

P17252

0

phosphorylation

up-regulates activity

0.394

Phosphorylation of RC3 by PKC alpha, beta, or gamma was stimulated by Ca2+, phospholipid, and diacylglycerol. A single site, Ser36, which is adjacent to the predicted calmodulin (CaM)-binding domain, was phosphorylated by these enzymes. Phosphorylation of RC3 by PKC or PKM, a protease-degraded PKC, was inhibited by CaM. The effect of CaM apparently targets at RC3, as phosphorylation of protamine sulfate by PKM was not inhibited by CaM.

SIGNOR-248913

Q13547

Q96EP1

0

polyubiquitination

down-regulates quantity by destabilization

0.394

Histone deacetylase 1 (HDAC1), which represses transcription by deacetylating histones, was newly isolated as a Chfr-interacting protein. Chfr binds and downregulates HDAC1 by inducing its polyubiquitylation, both in vitro and in vivo. Together, these results suggest that the ubiquitin ligase activity of Chfr targets HDAC1 for degradation.

SIGNOR-271465

Q07954

P12931

0

phosphorylation

up-regulates activity

0.394

We recently observed that the ldl receptor-related protein 1 (lrp-1) is tyrosine phosphorylated in v-src-transformed cells.Of the four tyrosine residues present in the cytoplasmic domain of lrp-1, only tyr 63 is phosphorylated by v-src in vivo or in vitro. Using fibroblasts deficient in src, yes and fyn, we were able to show that there are multiple kinases present in the cell that can phosphorylate lrp-1. Tyrosine-phosphorylated lrp-1 associates with shc, a ptb and sh2 domain containing signaling protein that is involved in the activation of ras

SIGNOR-101535

Q15438

P06241

0

phosphorylation

up-regulates activity

0.394

Fyn directly binds, phosphorylates, and activates cytohesin-1.

SIGNOR-280015

Q9H257

P40337

0

binding

down-regulates activity

0.393

We found that pVHL associates with the NF-kappaB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C terminus by CK2.

SIGNOR-257603

Q9BZL6

P17252

0

phosphorylation

up-regulates activity

0.393

Our data demonstrate that gastrin-stimulated PKD2 activation involves a heterotrimeric G alpha(q) protein as well as the activation of phospholipase C. Furthermore, we show that PKD2 can be activated by classical and novel members of the protein kinase C (PKC) family such as PKC alpha, PKC epsilon, and PKC eta.|The position of PKD2 phosphorylated at Ser876 and Ser706/Ser710 is indicated by anarrowhead.

SIGNOR-275955

Q9H4A3

P31749

0

phosphorylation

up-regulates

0.393

Phosphorylation of wnk1 on thr-58 contributes to sgk1 activation. these data suggest that activation of sgk1 by wnk1 requires the catalytic activity of akt.

SIGNOR-252481

O95967

P35555

0

binding

down-regulates activity

0.393

Fibulin-4 and -5 are extracellular glycoproteins with essential non-compensatory roles in elastic fiber assembly. Both fibulins differentially bound N-terminal fibrillin-1, which strongly inhibited their binding to lysyl oxidase and tropoelastin.

SIGNOR-251860

P23588

P31749

0

phosphorylation

up-regulates

0.393

Using an in vitro kinase assay, we found that pkb can directly phosphorylate eif4b on serine 422 (ser422). This was prevented by pretreatment of cells with the phosphatidylinositol 3-kinase (pi3k) inhibitor ly294002 or pharmacological inhibition of pkb. Phosphorylation regultes the activation of eukaryotic translation initiation factor 4b.

SIGNOR-252520

P46527

Q15418

0

phosphorylation

up-regulates activity

0.393

As for other PI3K effectors, RSK1 phosphorylates p27 at T198.|RSK1 overexpression increases p27pT198, p27-cyclin D1-Cdk4 complexes, and p27 stability.

SIGNOR-279653

Q99102

P42224

0

transcriptional regulation

up-regulates quantity by expression

0.393

Through promoter screening, overexpressing methods and luciferase reporter studies, we found that transcription factors CREB, Ets-1, Elk-1 and STAT1 can positively regulate MUC4 expression at the promoter and mRNA level.

SIGNOR-254099

Q13547

P17844

0

binding

up-regulates

0.393

Wt p68 co-immunoprecipitates efficiently with hdac1, the k53r p68 does not / sumoylation is important for the interaction of p68 with hdac1 and for transcriptional repression by p68

SIGNOR-153715

P29353

Q16832

0

binding

up-regulates

0.393

Collectively, our findings are consistent with the following mechanism for src-dependent ddr2 activation and signaling: 1) ligand binding promotes phosphorylation of tyr-740 in the ddr2 activation loop by src;2) tyr-740 phosphorylation stimulates intramolecular autophosphorylation of ddr2;3) ddr2 autophosphorylation generates cytosolic domain phosphotyrosines that promote the formation of ddr2 cytosolic domain-shc signaling complexes.

SIGNOR-140724

Q9Y618

P51843

0

binding

up-regulates activity

0.393

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-271785

Q8WUM4

P12931

0

phosphorylation

down-regulates activity

0.393

Src phosphorylation of Alix/AIP1 modulates its interaction with binding partners and antagonizes its activities. Phosphorylation of Alix by Src caused it to translocate from the membrane and cytoskeleton to the cytoplasm and reduced its interaction with binding partners SETA/CIN85, epidermal growth factor receptor, and Pyk2.

SIGNOR-263201

P00533

O14965

0

phosphorylation

up-regulates activity

0.393

Because AURKA associated with EGFR, we next investigated whether AURKA phosphorylates EGFR at Thr654 and Ser1046.|Protein phosphorylation profiling using an in situ proximity ligation assay: phosphorylation of AURKA-elicited EGFR-Thr654 and EGFR-Ser1046 in lung cancer cells.

SIGNOR-279589

Q06413

Q92585

0

binding

up-regulates

0.393

Unexpectedly, however, emerging evidence implicate maml proteins as exciting key transcriptional co-activators in other signal transduction pathways including: muscle differentiation and myopathies (mef2c), tumor suppressor pathway (p53) and colon carcinoma survival (beta-catenin).

SIGNOR-144913