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mechanism
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effect
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10 values
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14
Q9UPR3
Q9BY41
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
P16144
Q99704
2
binding
down-regulates activity
0.2
Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation
SIGNOR-257689
P14136
Q9UQM7
0
phosphorylation
down-regulates activity
0.427
On the other hand, GFAP was phosphorylated to approximately 1.9 mol of phosphate/mol of GFAP by Ca(2+)-CaM-dependent protein kinase II, and this phosphorylation did induce disassembly of the filament. Sequential analysis of the purified phosphopeptides revealed that only Ser8 on GFAP was phosphorylated by cdc2 kinase, ...
SIGNOR-250626
Q9Y5I2
Q9Y5G5
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-265702
P04899
P61073
2
binding
up-regulates activity
0.484
Using this model, we have reported that CXCL12 activates Gi1, Gi2, or Gi3 heterotrimeric G proteins in a concentration-dependent manner
SIGNOR-278103
Q5SQI0
Q6PEY2
1
acetylation
up-regulates quantity by stabilization
0.267
Alpha-Tubulin acetyltransferase (alphaTAT1) is the major α-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes.|The tubulin subunits of microtubules are acetylated, and lysine-40 (K40) of the alpha-tubulin subunit ...
SIGNOR-272248
Q12857
Q9Y6N7
1
transcriptional regulation
up-regulates quantity
0.2
For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)
SIGNOR-268893
P49840
Q9NZQ7
1
phosphorylation
down-regulates quantity by destabilization
0.2
We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation.
SIGNOR-277552
Q9Y5G8
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-265717
P48058
P17612
0
phosphorylation
up-regulates
0.429
We found that pka phosphorylation of the ampa receptor subunits glur4 and glur1 directly controlled the synaptic incorporation of ampa receptors in organotypic slices from rat hippocampus.
SIGNOR-97550
Q96G30
P32245
2
binding
down-regulates activity
0.504
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...
SIGNOR-252363
Q9H0E2
Q9NPH3
2
binding
down-regulates activity
0.638
Binding of IL-1 to its receptor results in rapid assembly of a membrane-proximal signalling complex that consists of two different receptor chains (IL-1Rs), IL-1RI and IL-1RAcP, the adaptor protein MyD88, the serine/threonine kinase IRAK and a new protein, which we have named Tollip. Here we show that, before IL-1β tre...
SIGNOR-251979
Q8IV61
Q04759
0
phosphorylation
up-regulates
0.328
Activation of rasgrp3 by phosphorylation of thr-133 is required for b cell receptor-mediated ras activation. our data suggest that pkc, after being activated by diacylglycerol, phosphorylates rasgrp3, thereby contributing to its full activation.
SIGNOR-130490
Q9Y6Y9
P09429
2
binding
up-regulates activity
0.63
Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2-deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR...
SIGNOR-252058
Q9HCX4
Q13976
0
phosphorylation
up-regulates activity
0.2
In vitro and in vivo kinase assays have revealed that cGK-Iα phosphorylates mouse TRPC7 but not mouse TRPC3. Site-directed mutagenesis analysis revealed that TRPC7 was phosphorylated by cGK-Iα at threonine 15. Phosphorylation of TRPC7 significantly suppressed carbachol-induced calcium influx and CREB phosphorylation. ...
SIGNOR-263184
Q9BXM7
P62987
1
phosphorylation
up-regulates
0.385
Here we report that ubiquitin is the genuine substrate of PINK1. PINK1 phosphorylated ubiquitin at Ser 65 both in vitro and in cells, and a Ser 65 phosphopeptide derived from endogenous ubiquitin was only detected in cells in the presence of PINK1 and following a decrease in mitochondrial membrane potential.
SIGNOR-270342
P01266
P27695
0
transcriptional regulation
up-regulates quantity by expression
0.2
In co-transfection experiments, Ref-1 increases the Pax-8 activating effect on thyroglobulin promoter.
SIGNOR-271694
O15273
P49841
0
phosphorylation
down-regulates quantity by destabilization
0.2
GSK-3beta phosphorylates FBXL21 and TCAP to activate FBXL21-mediated, phosphodegron-dependent TCAP degradation.|These results show direct GSK-3beta phosphorylation of TCAP S157 and FBXL21 T33 sites.
SIGNOR-264852
Q13464
P61586
2
binding
up-regulates activity
0.81
Planar cell polarity (pcp) signalling triggers activation of the small gtpases rhoa and rac1, which in turn activate rho kinase (rock) and jun-n-terminal kinase (jnk), respectively, leading to actin polymerization and microtubule stabilization.
SIGNOR-199542
P12830
Q15139
0
phosphorylation
up-regulates
0.451
Our study has identified e-cadherin as a novel substrate of pkd1, and phosphorylation of e-cadherin by pkd1 is associated with increased cellular aggregation and decreased cellular motility in prostate cancer.
SIGNOR-133856
O43896
Q9NRW1
1
relocalization
up-regulates quantity
0.2
Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentr...
SIGNOR-266878
Q9HD90
O00712
0
transcriptional regulation
up-regulates quantity
0.2
For example, within the NFI targetome, we identified 6 collagen genes, 13 genes encoding potassium channel or glutamate receptor subunits and a range of factors related to axon guidance (e.g. Slit1, Robo1, Epha4, Epha5, Epha8)
SIGNOR-268898
Q12913
P08581
1
dephosphorylation
down-regulates activity
0.608
When co-expressed in 293 cells, the full-length substrate-trapping mutant form of DEP-1 formed a stable complex with the chimeric receptor colony stimulating factor 1 (CSF)-Met and wild type DEP-1 dephosphorylated CSF-Met. Furthermore, we observed that DEP-1 preferentially dephosphorylated a Gab1 binding site (Tyr(1349...
SIGNOR-248702
O14641
O14641
2
binding
up-regulates activity
0.2
Dix domain of dvl2 mediates dynamic polymerization, which is essential for the signaling activity of dvl2.
SIGNOR-155224
P27361
P35236
1
phosphorylation
up-regulates activity
0.693
First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185.|
SIGNOR-249475
Q13315
P20823
1
phosphorylation
up-regulates
0.256
Serine 249 phosphorylation by atm protein kinase regulates hepatocyte nuclear factor-1_ transactivation
SIGNOR-205087
P06241
P11912
1
phosphorylation
up-regulates activity
0.596
Lyn and Fyn phosphorylated the CD79a cytoplasmic portion of the fusion proteins well, with >80% of phosphorylation occurring at Y182. CD79a and CD79b function as transducers of B cell antigen receptor signals via a cytoplasmic sequence, termed the immunoreceptor tyrosine-based activation motif (ITAM).
SIGNOR-251153
Q9BT67
P46934
1
relocalization
up-regulates activity
0.589
Ndfip1 is primarily localized in the Golgi apparatus where it recruits Nedd4-2 to mediate the degradation of mature hERG proteins during channel trafficking to the plasma membrane. Although Ndfip2 directs Nedd4-2 to the Golgi apparatus, it also recruits Nedd4-2 to the multivesicular bodies (MVBs), which may impair MVB ...
SIGNOR-260997
Q92769
Q5VUA4
2
binding
up-regulates activity
0.329
A central domain of TZF is required for repression of AR-mediated transactivation. The results revealed that HDAC2 was coimmunoprecipitated with TZF (Fig. 6A), These results indicate that AR, TZF and HDAC2 form a ternary complex during the repression of AR-mediated transactivation.
SIGNOR-261188
P43119
P38405
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- signali...
SIGNOR-256949
Q9H3R0
P10275
2
binding
up-regulates activity
0.2
JMJD2C was found to be co-localized with AR and LSD1 in the epithelium of prostate carcinoma and normal prostate cells. For the detailed mechanism, JMJD2C, AR and LSD1 assembled on the chromatin to remove the methyl groups from mono-, di- and trimethylated H3K9. Importantly, JMJD2C specifically removed the demethylatio...
SIGNOR-263879
P09341
P17612
2
binding
down-regulates
0.2
As pka suppresses the activity of gli, smo might use the stimulation of pi3k by galfai and gbetagamma subu- nits to block pka in cells that have high levels of camp.
SIGNOR-152594
Q03113
P32238
2
binding
up-regulates activity
0.25
Our studies indi-cate that CCK-A receptors inserted into NIH3T3 cellsalso activate RhoA through G12/13
SIGNOR-278063
P03209
Q14653
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-266644
Q53ET0
Q9Y2K2
0
phosphorylation
down-regulates activity
0.635
We found that QSK and SIK phosphorylated TORC2 at Ser171 as well as at least two additional residues, namely Ser70 and Ser348|QIK also phosphorylates the CREB co-activator TORC2, in unstimulated cells, to sequester it in the cell cytoplasm, thereby inhibiting CREB-dependent gene-expression
SIGNOR-249170
P42681
Q13094
1
phosphorylation
up-regulates
0.728
Resting lymphocyte kinase (rlk/txk) targets lymphoid adaptor slp-76 in the cooperative activation of interleukin-2 transcription in t-cells. In this study, we report that rlk phosphorylates slp-76 at its n-terminal yesp/yepp sites. A third tyrosine within the amino-terminal region (y145) appears to be the most importan...
SIGNOR-44669
P04637
Q07812
2
binding
up-regulates
0.753
P53 also accumulates in the cytoplasm where it directly activates bax to promote mitochondrial outer membrane permeabilization.
SIGNOR-140242
P33981
P21589
1
phosphorylation
up-regulates activity
0.2
Intermolecular NTE phosphorylation by Mps1 requires a topology in which sites proximal to the NTE interact with the active Mps1 in order to promote phosphorylation.
SIGNOR-280157
O75030
P20265
0
transcriptional regulation
up-regulates quantity by expression
0.437
We further demonstrate that BRN2 induces MITF transcription through a binding site located at ˆ’50/ˆ’36 of the MITF promoter
SIGNOR-249616
P08247
Q05193
2
binding
up-regulates activity
0.333
The GTPase dynamin I is required for synaptic vesicle (SV) endocytosis. Our observation that dynamin binds to the SV protein synaptophysin in a Ca2+-dependent fashion suggested the possibility that a dynamin/synaptophysin complex functions in SV recycling.
SIGNOR-264119
O43524
P27361
0
phosphorylation
down-regulates quantity by destabilization
0.595
Phosphorylation of foxo3a by erk1/2 at residues ser 294, ser 344 and ser 425 increases foxo3amdm2 interaction and enhances foxo3a degradation via an mdm2-dependent ubiquitin-proteasome pathway
SIGNOR-184569
P18564
O14713
2
binding
down-regulates activity
0.287
Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation
SIGNOR-257662
Q9BQQ3
P28482
0
phosphorylation
down-regulates activity
0.27
Here we show that GRASP65 is phosphorylated on serine 277 in interphase cells, and this is strongly enhanced in response to the addition of serum or epidermal growth factor. This is directly mediated by ERK suggesting that GRASP65 has some role in growth factor signal transduction. These results argue against Ser-277 p...
SIGNOR-262841
Q16875
Q9P1W9
0
phosphorylation
up-regulates quantity by stabilization
0.2
We used biochemical methods to determine that PIM2 can directly bind and change the phosphorylation of PFKFB3 at Ser478 to enhance PFKFB3 protein stability through the ubiquitin-proteasome pathway.
SIGNOR-277554
P08559
P54646
0
phosphorylation
up-regulates activity
0.2
AMPKα phosphorylates PDHA subunit on Ser295 and Ser314 to activate PDH complex
SIGNOR-276838
O75030
P16220
0
transcriptional regulation
up-regulates quantity by expression
0.633
Therefore, the molecular steps linking cAMPto melanogenesis up-regulation appear currently better elucidated. cAMP activates PKA, and PKA phosphorylates and activates CREB which, when activated, binds to the CRE domain present in the microphthalmia promoter,thereby up-regulating its transcription.
SIGNOR-249619
O00327
P37231
0
transcriptional regulation
up-regulates quantity by expression
0.399
 Rosiglitazone treatment induced aortic expression of Bmal1 mRNA, and ChIP and promoter assays revealed that Bmal1 is a direct PPARgamma target gene. These studies have uncovered a role for vascular PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms.
SIGNOR-268026
P31749
P98170
1
phosphorylation
up-regulates quantity by stabilization
0.618
Akt, including akt1 and akt2, interacts with and phosphorylates x-linked inhibitor of apoptosis protein (xiap) at residue serine-87 in vitro and in vivo. Phosphorylation of xiap by akt protects xiap from ubiquitination and degradation in response to cisplatin.
SIGNOR-119488
Q15276
P20339
2
binding
up-regulates
0.928
We have previously shown that rab5, which regulates various steps of transport along the early endocytic pathway, is activated by a complex consisting of rabex-5, a rab5 nucleotide exchange factor, and the effector rabaptin-5.
SIGNOR-109352
Q9HC56
P05556
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.
SIGNOR-269035
O95837
O60755
2
binding
up-regulates activity
0.289
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- signali...
SIGNOR-257206
P17181
P01574
2
binding
up-regulates
0.867
Ifn-alpha, ifn-beta, and ifn-omega, induce somewhat different cellular effects but act through a common receptor complex, ifnar, composed of subunits ifnar-1 and ifnar-2.
SIGNOR-104663
P47710
Q04206
1
phosphorylation
up-regulates
0.2
Phosphorylation of serine 529 of p65 is mediated by casein kinase ii, but is prevented in nonstimulated cells by the interaction with ikba
SIGNOR-171222
Q15303
Q96JA1
0
ubiquitination
down-regulates
0.608
We report upregulation of lrig1 transcript and protein upon egf stimulation, and physical association of the encoded protein with the four egfr orthologs of mammals. Upregulation of lrig1 is followed by enhanced ubiquitylation and degradation of egfr. The underlying mechanism involves recruitment of c-cbl, an e3 ubiqui...
SIGNOR-139954
Q9HA47
Q13315
0
phosphorylation
down-regulates quantity by destabilization
0.2
ATM also phosphorylates UCK1 at S145, significantly enhancing the KLHL2-UCK1 complex formation|We demonstrated that the ubiquitin E3 ligase KLHL2 interacted with UCK1 and mediated its polyubiquitination at the K81 residue and degradation.
SIGNOR-275963
P12931
P46934-4
1
phosphorylation
up-regulates activity
0.417
Activation of c-Src by epidermal growth factor (EGF) also promoted tyrosine phosphorylation and enhanced the activity of NEDD4. 
SIGNOR-276860
P26599
P01106
0
transcriptional regulation
up-regulates quantity by expression
0.438
We also demonstrate that the oncogenic transcription factor c-Myc upregulates transcription of PTB, hnRNPA1 and hnRNPA2,
SIGNOR-268689
P15976
Q01196
2
binding
up-regulates activity
0.643
We and others have previously shown that RUNX1 and GATA-1 physically interact and cooperate in the activation of megakaryocytic promoters such as alpha IIb integrin and glycoprotein Ibalpha. In particular, we will elaborate on recent data which suggest that GATA-1 targets RUNX1 for modification, in particular phosphor...
SIGNOR-254194
Q92823
P54762
0
phosphorylation
up-regulates activity
0.411
EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively acti...
SIGNOR-262862
Q16552
Q9BYH8
0
transcriptional regulation
up-regulates quantity by expression
0.381
In cooperation with RORγt and RORα, IκBζ enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. 
SIGNOR-266210
Q02763
O95841
2
binding
up-regulates
0.506
In experiments with human endothelial cell lines, ang3 was identified as an antagonist of tie2 and ang4 was identified as an agonist of tie2.
SIGNOR-127354
O75030
P28482
0
phosphorylation
down-regulates
0.705
The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73the results suggested that s1p re...
SIGNOR-75030
O15530
P31751
1
phosphorylation
up-regulates activity
0.732
Akt1 and akt2 are phosphorylated and activated by the protein kinase pdk1 at thr-308 or thr-309, respectively, in the activation t-loop, and further activation occurs through phosphorylation at ser-473 or ser-474, respectively. Pdk1 phosphorylates akt-2 at thr 309 in the catalytic domain, leading to enzymatic activatio...
SIGNOR-134485
Q16665
P46531
0
relocalization
up-regulates activity
0.649
The notch intracellular domain interacts with hif-1alpha and hif-1alpha is recruited to notch-responsive promoters upon notch activation under hypoxic conditions.
SIGNOR-141315
P06493
P49821
1
phosphorylation
up-regulates activity
0.2
Here, we show that a fraction of cyclin B1/Cdk1 proteins localizes to the matrix of mitochondria and phosphorylates a cluster of mitochondrial proteins, including the complex I (CI) subunits in the respiratory chain. Cyclin B1/Cdk1-mediated CI phosphorylation enhances CI activity, whereas deficiency of such phosphoryla...
SIGNOR-275594
P53350
O15350
1
phosphorylation
down-regulates
0.51
P73-mediated transcriptional activity is negatively regulated by polo-like kinase 1. tap73 is phosphorylated by this kinase on threonine-27 (thr-27) within the ta domain.
SIGNOR-178253
P21796
Q96A26
2
binding
up-regulates activity
0.2
HGTD-P was coprecipitated with VDAC but not with ANT or cyclophilin D (Fig. 7A, left upper panel).|However, it is not clear at present whether HGTD-P participates directly in channel formation in association with VDAC or modulates its channel-forming activity.
SIGNOR-260293
Q13627
Q05193
1
phosphorylation
down-regulates
0.416
Mnb/dyrk1a was shown to phosphorylate dynamin 1 and alter its interactions with several sh3 domain-containing endocytic accessory proteins.Phosphorylation At s795 and s857 was confirmed in full-length dynamin 1, and s857 was subsequently determined to be the major mnb/dyrk1a phosphorylation site in vitro. Phosphorylati...
SIGNOR-127440
O00399
P53350
2
binding
up-regulates activity
0.374
Here, we show that the p27/p25 heterodimer undergoes mitotic phosphorylation by cyclin‐dependent kinase 1 (Cdk1) at a single site, p27 Thr186, to generate an anchoring site for polo‐like kinase 1 (Plk1) at kinetochores.
SIGNOR-264798
Q99538
Q6R6M4
0
deubiquitination
down-regulates quantity by destabilization
0.309
We demonstrate that TRAF6 ubiquitinates the proform of AEP through K63-linked polyubiquitin, reversible by USP17, and forms a complex with HSP90α to subsequently promote pro-AEP intracellular stability as well as secretion. We now present evidence that AEP is a substrate for TRAF6 ubiquitination, resulting in AEP/TRAF6...
SIGNOR-272854
Q05682
P17252
0
phosphorylation
down-regulates
0.357
Phosphorylation of both intact caldesmon and of its c-terminal fragment (658c), containing residues 658-756, significantly decreased their ability to inhibit acto-heavy meromyosin atpase.
SIGNOR-36792
O94782
Q8WYQ5
1
deubiquitination
up-regulates quantity by stabilization
0.2
 Specifically, radiation-induced ATM-dependent phosphorylation of DGCR8 at serine 677 facilitates USP51 to bind, deubiquitinate, and stabilize DGCR8, which leads to the recruitment of DGCR8 and DGCR8's binding partner RNF168 to MDC1 and RNF8 at DSBs. 
SIGNOR-277308
P12931
Q16832
1
phosphorylation
up-regulates
0.38
Here, using baculoviral co-expression of the ddr2 cytosolic domain and src, we show that src targets three tyrosine residues (tyr-736, tyr-740, and tyr-741) in the activation loop of ddr2 for phosphorylation. This phosphorylation by src stimulates ddr2 cis-autophosphorylation of additional tyrosine residues.
SIGNOR-140767
P14921
P49841
0
phosphorylation
up-regulates quantity by stabilization
0.2
Here, we show that ETS1 forms a complex with glycogen synthase kinase-3β (GSK3β). Specifically, GSK3β-mediated phosphorylation of ETS1 at threonine 265 and serine 269 promoted protein stability, induced the transcriptional activation of matrix metalloproteinase (MMP)-9, and increased cell migration.
SIGNOR-277560
O95837
Q9HBW0
2
binding
up-regulates activity
0.484
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- signali...
SIGNOR-257431
Q5T7P8
P05771
0
phosphorylation
up-regulates activity
0.2
We found by site-directed mutagenesis that Thr418 and/or Thr419 in the polybasic region (KKKTTIK) of the C2B domain--a key region for the function of synaptotagmins--are the PKC target that regulates its inhibitory effect on acrosomal exocytosis. Similarly, we showed that Thr284 in the polybasic region of C2A (KCKLQTR)...
SIGNOR-273565
Q96GF1
Q12981
1
polyubiquitination
up-regulates activity
0.533
RNF185 functions as a ubiquitin E3 ligase, enabling BNIP1-p62 interaction. Here we show that human RNF185 is a mitochondrial ubiquitin E3 ligase that regulates selective mitochondrial autophagy in cultured cells.  Human BNIP1 colocalizes with RNF185 at mitochondria and is polyubiquitinated by RNF185 through K63-based u...
SIGNOR-271931
Q00535
Q9Y696
1
phosphorylation
up-regulates quantity by stabilization
0.2
These results confirm that CDK5 phosphorylates CLIC4 at serine 108.|We found that activated CDK5 phosphorylated serine 108 in CLIC4, increasing CLIC4 protein stability, and accumulation.
SIGNOR-279451
P01112
Q5VWQ8
0
gtpase-activating protein
down-regulates activity
0.6
The GAP domain of DAB2IP is homologous to other Ras-GAPs, such as GAP120 and neurofibromin (NF1), and can stimulate the GTPase activity of RAS proteins both in vitro and in cancer cell lines. DAB2IP is able to stimulate in vitro and in vivo the GTPase activity of RAS proteins (H-Ras, K-Ras, and N-Ras) facilitating GTP ...
SIGNOR-254745
P19793
P37231
2
binding
up-regulates
0.743
Although the three ppar subtypes are closely related and bind to similar dna response elements as heterodimers with the 9-cis retinoic acid receptor rxr, each subserves a distinct physiology
SIGNOR-105445
Q5UE93
P31749
0
phosphorylation
up-regulates activity
0.45
P84 forms a negative regulatory complex with p110gamma to control PI3Kgamma signalling during cell migration|However, phosphorylation at this site was confirmed using an in vitro kinase assay in which Akt kinase was shown to readily phosphorylate Thr607 using a p84 peptide (Figure 1e), where Thr607 in conjunction with ...
SIGNOR-275722
O15392
P53350
0
phosphorylation
up-regulates
0.583
Thus, we conclude that plk1-mediated phosphorylation of sur at ser20 is critical for accurate chromosome segregation|SUR (survivin)
SIGNOR-170460
P62136
P38398
1
dephosphorylation
down-regulates activity
0.377
Protein kinases involved in the DNA damage checkpoint control, such as ATM, ATR, and hCds1/Chk2, have been shown to phosphorylate and activate BRCA1 upon DNA damage. |Altogether, these results indicate that PP1α specifically dephosphorylates BRCA1 at multiple serine sites, including S988 [12], S1423, and S1524.
SIGNOR-248560
P15884
P35222
2
binding
up-regulates activity
0.69
beta-catenin interacts with the TCF/Lef family transcription factors.
SIGNOR-178042
Q8N726
Q9UHC7
0
polyubiquitination
down-regulates quantity by destabilization
0.366
Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation.The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.
SIGNOR-272036
Q99986
Q12888
1
phosphorylation
up-regulates
0.399
The kinase vrk1 is activated by dna double strand breaks induced by ionizing radiation (ir) and specifically phosphorylates 53bp1 in serum-starved cells./ Vrk1 knockdown resulted in the defective formation of 53bp1 foci in response to ir both in number and size
SIGNOR-197625
P08069
Q13191
0
ubiquitination
down-regulates quantity by destabilization
0.422
The ubiquitin ligase Cbl-b also ubiquitinated and degraded IGF-IR and inhibited the Akt/ERK-miR-200c-ZEB2 axis, leading to the repression of IGF-I-induced EMT.
SIGNOR-278607
P11166
P27105
2
binding
down-regulates activity
0.527
Similar to the results obtained in the RBC, Glut1 and stomatin immunoprecipitated with each other in lysates of Clone 9 cells. The above results suggest that stomatin is closely associated with Glut1 in the plasma membrane and that overexpression of stomatin results in a depression in the basal rate of glucose transpor...
SIGNOR-261278
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 acti...
SIGNOR-157167
Q06830
P06239
0
phosphorylation
down-regulates activity
0.2
Inactivation of peroxiredoxin I by phosphorylation allows localized H(2)O(2) accumulation for cell signaling. To determine whether Prxs are phosphorylated, we subjected recombinant human PrxI and II to an in vitro kinase assay with two nonreceptor PTKs, Lck and Abl, in the presence of [γ-32P]ATP. Both PTKs phosphorylat...
SIGNOR-276277
P00519
Q03468
1
phosphorylation
up-regulates activity
0.271
N-terminal region of CSB interacts with the SH3 domain of c-Abl in vitro and in vivo. In addition, c-Abl kinase phosphorylates CSB at Tyr932. our results suggest that c-Abl interacts with and tyrosine phosphorylates CSB. This interaction may play an important role in the response to oxidative stress, resulting in activ...
SIGNOR-251933
Q8WUJ0
Q969H0
2
binding
down-regulates activity
0.346
STYX acts as a direct inhibitor of FBXW7, affecting the cellular levels of its substrates. Furthermore, we find that levels of STYX and FBXW7 are anti-correlated in breast cancer patients,
SIGNOR-251663
P48431
O00308
0
ubiquitination
down-regulates quantity
0.361
Among the four E3 ligases, only WWP2 knockdown was found to increase SOX2 protein levels in GSCs (Fig.\u00a04A).|We first verified that WWP2 ubiquitinates SOX2 in vitro.
SIGNOR-278798
P20396
P23769
0
transcriptional regulation
up-regulates quantity by expression
0.263
The rat prepro-TRH gene is activated by GATA2.
SIGNOR-267259
Q96HE7
Q9BS26
2
binding
up-regulates quantity by stabilization
0.2
Here, we report the functional characterization of a novel UPR-induced ER resident protein (ERp44) that forms mixed disulfides with both hEROs, as well as with partially unfolded Ig subunits.
SIGNOR-261049
P07948
P31995
1
phosphorylation
up-regulates activity
0.2
Fyn and Blk definitely phosphorylate Y-282 in the ITAM of FcgRIIa/c, whereas the non-ITAM tyrosine residue (Y-275) becomes phosphorylated by Syk, as the phosphorylation of double point mutants shows. In addition to these tyrosine residues, Fyn, Blk, and Syk might phosphorylate the most C-terminal tyrosine residue (Y-29...
SIGNOR-262676
O14641
Q96GF1
0
polyubiquitination
down-regulates quantity by destabilization
0.466
The E3 ligase RNF185 negatively regulates osteogenic differentiation by targeting Dvl2 for degradation. Overexpression of RNF185 decreases the exogenous and endogenous level of Dvl2, promotes the ubiquitination and degradation of Dvl2
SIGNOR-272173
Q9GZR7
Q00987
0
polyubiquitination
up-regulates activity
0.334
MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early st...
SIGNOR-272845
Q13131
Q9P1W9
0
phosphorylation
down-regulates activity
0.2
Specifically, we found that PIM2 bound to AMPKα1, and directly phosphorylated it on Thr467. Phosphorylation of AMPKα1 by PIM2 led to decreasing AMPKα1 kinase activity, which in turn promoted aerobic glycolysis and tumor growth.
SIGNOR-277471
P24530
P63096
2
binding
up-regulates activity
0.449
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- signali...
SIGNOR-257053