IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
Q53HL2
P33981
0
phosphorylation
up-regulates
0.461
First, we confirmed that wild-type borealin is phosphorylated at the previously described sites t88, t94, t169, and t230 when present in complex with survivin borealin might be a substrate for mps1. In the case of wild-type borealin, the fast exchange between the monomeric and dimeric forms may allow mps1 to phosphorylate the monomer. In turn, mps1 may regulate borealin function by unfolding the c-terminal domain and/or shifting the population to the monomeric form.
SIGNOR-186151
P28482
P07101
1
phosphorylation
up-regulates
0.441
Mitogen-activated protein-kinase (map) kinase-activated protein kinases 1 and 2 (mapkap kinase-1, mapkap kinase-2), were found to phosphorylate bacterially expressed human tyrosine hydroxylase in vitro at comparable rates to other proteins thought to be physiological substrates of these protein kinases.The effect on activity of phosphorylating both ser31 and ser40 was not additive. The possible roles of mapkap kinase-1, mapkap kinase-2 and map kinase in the regulation of tyrosine hydroxylase in vivo are discussed.
SIGNOR-34674
Q8IYJ3
P31749
0
phosphorylation
down-regulates quantity
0.355
By mutagenesis analysis and subsequent immunoprecipitation (IP), we established that Akt phosphorylates JFC1 at serine 241. Phosphorylation did not alter the ability of JFC1 to bind to Rab27a. Instead, phosphorylation by Akt dramatically decreased when JFC1 was bound to Rab27a. Finally, we show that as a consequence of in vivo phosphorylation, JFC1 dissociates from the membrane, promoting JFC1 redistribution to the cytosol.
SIGNOR-273540
P12931
Q12879
1
phosphorylation
up-regulates activity
0.567
To gain further insight into the roles of Src and Fyn in the phosphorylation and regulation of the NMDA receptor, we have characterized the tyrosine phosphorylation of NR2A and NR2B by exogenous Src and FynIn the case of NR2A, three potential tyrosine phosphorylation sites have been proposed: Tyr1105, Tyr1267 and Tyr1387 (Zheng et al. 1998; Bi et al. 2000), all of which are similarly located in the C-terminal, cytoplasmic domain.
SIGNOR-247167
Q14524
P06241
0
phosphorylation
down-regulates
0.293
This study addresses the effects of the src family tyrosine kinase fyn on na(v)1.5 cardiac sodium channels. Sodium currents were acquired by whole cell recording on hek-293 cells transiently expressing na(v)1.5. Acute treatment of cells with insulin caused a depolarizing shift in steady-state inactivation, an effect eliminated by the src-specific tyrosine kinase inhibitor pp2 we provide evidence that this linker is a substrate for fyn in vitro, and that y1495 is a preferred phosphorylation site.
SIGNOR-135600
Q86TM6
P05198
1
ubiquitination
down-regulates quantity by destabilization
0.2
HRD1 overexpression also decreased the expression of eIF2alpha and p-eIF2alpha in HKC-8 cells.|HRD1 promoted eIF2alpha ubiquitylation and degradation, thereby providing a protective mechanism that suppressed tubular epithelial cell apoptosis.
SIGNOR-278671
P45983
Q15672
1
phosphorylation
up-regulates
0.308
Phosphorylation of serine 68 of twist1 by mapks stabilizes twist1 protein and promotes breast cancer cell invasiveness.
SIGNOR-173417
P55211
Q6UXS9
0
cleavage
up-regulates
0.2
Caspase-12 specifically cleaves and activates procaspase-9 in cytosolic extracts. Results suggest that caspase-12 can activate caspase-9 without involvement of cytochromec.
SIGNOR-90318
Q96GD4
O95235
1
phosphorylation
down-regulates activity
0.781
We identify MKlp2 as an essential protein for promoting abscission, which may regulate tethering and stabilizing of the PM to the microtubule cytoskeleton. Aurora B phosphorylation of MKlp2 S878 in the LAM is a key inhibitory signal for abscission. Conversely, B56-PP2A promotes abscission by opposing Aurora B phosphorylation of MKlp2 S878.
SIGNOR-262659
P45983
P35568
1
phosphorylation
down-regulates activity
0.771
Insulin also activates jnk, erk, pkc and mtor, which induce the phosphorylation of irs1 on serine residues 307, 612 and 632 and inhibit its functions. Our results indicate that the insulin-stimulated degradation of irs-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the ser(312) phosphorylation of irs-1.
SIGNOR-96948
P35813
P27986
1
dephosphorylation
up-regulates activity
0.324
Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes|PP2Cα dephosphorylates the p85 subunit of PI3K, and dephosphorylation of the p85 subunit of PI3K at Ser608 increases its activity
SIGNOR-248489
P17612
P54646
1
phosphorylation
down-regulates
0.42
Pka associates with and phosphorylates ampk?1 At ser-173 to impede threonine thr-172 phosphorylation and thus activation of ampk1 by lkb1 in response to lipolytic signals
SIGNOR-161860
O94806
O96013
1
phosphorylation
up-regulates activity
0.252
PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1)
SIGNOR-275931
Q9Y2N7
Q16665
1
transcriptional regulation
down-regulates quantity by repression
0.524
None of the long HIF-3α variants was capable of efficient induction of an HRE reporter in overexpression experiments, but instead inhibited the transcriptional activation of the reporter by HIF-1 and HIF-2. 
SIGNOR-261615
O15055
Q9Y2K2
0
phosphorylation
down-regulates quantity by destabilization
0.2
In the current study, we found that SIK3 promotes phosphorylation of PER2 and regulates the abundance of the protein by accelerating its degradation.
SIGNOR-279570
Q9NR19
Q9GZQ8
1
transcriptional regulation
up-regulates quantity by expression
0.2
As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;
SIGNOR-276562
Q07343
P17612
0
phosphorylation
up-regulates activity
0.605
PKA-mediated phosphorylation of Ser-56 in UCR1 of PDE4B4 leads to activation of this long isoform
SIGNOR-250024
Q8WYQ5
O94782
0
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
P46527
P11309
0
phosphorylation
down-regulates activity
0.382
We show, herein, that all the pim family members (pim1, pim2, and pim3) bind to and directly phosphorylate the cyclin-dependent kinase inhibitor p27(kip1) at threonine-157 and threonine-198 residues in cells and in vitro.|Pim kinases promote cell cycle progression and tumorigenesis by down-regulating p27(Kip1) expression at both transcriptional and posttranslational levels.
SIGNOR-179300
P45983
P37231
1
phosphorylation
down-regulates activity
0.527
The a/b domain of human ppargamma1 was phosphorylated in vivo, and this was abolished either by mutation of serine 84 to alanine (s84a) or coexpression of a phosphoprotein phosphatase. In vitro, this domain was phosphorylated by erk2 and jnk, and this was markedly reduced in the s84a mutant. Thus, phosphorylation of a mitogen-activated protein kinase site in the a/b region of ppargamma inhibits both ligand-independent and ligand-dependent transactivation functions.
SIGNOR-46518
P38936
Q9BV68
0
polyubiquitination
down-regulates quantity by destabilization
0.331
E3 ubiquitin ligase RNF126 promotes cancer cell proliferation by targeting the tumor suppressor p21 for ubiquitin-mediated degradation.We showed that RNF126 interacts with p21 and RNF126 overexpression increased p21 protein ubiquitination in an E3 ligase activity-dependent manner.
SIGNOR-272033
Q00987
P62136
0
dephosphorylation
up-regulates quantity by stabilization
0.356
Three phosphorylation sites identified are Ser342, Ser367, and Ser403. In the present study, we identify protein phosphatase 1 (PP1) as a negative regulator in the p53 signaling pathway. PP1 directly interacts with Mdmx and specifically dephosphorylates Mdmx at Ser367. The dephosphorylation of Mdmx increases its stability and thereby inhibits p53 activity.
SIGNOR-248566
P15311
Q13464
0
phosphorylation
up-regulates
0.732
Activation of ezrin is mediated by initial pip2 binding and subsequent phosphorylation of threonine 567. We performed an in vitro kinase assay with 80 selected kinases on an ezrin peptide containing the t567 phosphorylation site (figure 3a). In this screen, we identified the mst and rock kinases as the most potent kinases for the ezrin peptide
SIGNOR-185567
P04049
P31749
0
phosphorylation
down-regulates
0.7
Akt and protein kinase a (pka) phosphorylate s259 on raf-1 and inhibit its activity.
SIGNOR-147963
P31749
Q9UBP6
1
phosphorylation
down-regulates
0.335
The trna methylase mettl1 is phosphorylated and inactivated by pkb and rsk in vitro and in cells
SIGNOR-24994
P0DMV8
Q9HC98
0
phosphorylation
up-regulates activity
0.425
Mitotic phosphorylation of Hsp72 by the kinase NEK6 at Thr66 located in the NBD promotes the localization of Hsp72 to the mitotic spindle and is required for efficient spindle assembly and chromosome congression and segregation. 
SIGNOR-273885
O14950
Q13418
0
phosphorylation
up-regulates activity
0.314
Integrin-linked kinase cdna was cloned, sequenced, expressed in e. coli, and shown to phosphorylate myosin light chain in the absence of ca(2+) at ser(19) and thr(18). Smooth muscle contraction follows an increase in cytosolic Ca(2+) concentration, activation of myosin light chain kinase, and phosphorylation of the 20-kDa light chain of myosin at Ser(19).Smooth muscle contraction follows an increase in cytosolic Ca(2+) concentration, activa
SIGNOR-106427
Q6WKZ4
Q7KZI7
0
phosphorylation
up-regulates quantity
0.341
We have now found that MARK2 phosphorylates Rab11-FIP1B/C at serine 234 in a consensus site similar to that previously identified in Rab11-FIP2.
SIGNOR-273676
Q04206
Q9UHD2
0
phosphorylation
up-regulates
0.614
Chromatographic fractionation of cell extracts allowed the identification of two distinct enzymatic activities phosphorylating ser-536. Peak 1 represents an unknown kinase, whereas peak 2 contained ikkalpha, ikkbeta, ikkepsilon, and tbk1. collectively, our results provide evidence for at least five kinases that converge on ser-536 of p65 and a novel function for this phosphorylation site in the recruitment of components of the basal transcriptional machinery to the interleukin-8 promoter.
SIGNOR-129951
Q16695
P49336
0
phosphorylation
down-regulates activity
0.2
However, within T/G-Mediator, cdk8 phosphorylates serine-10 on histone H3, which in turn stimulates H3K14 acetylation by GCN5L within the complex. Tandem phosphoacetylation of H3 correlates with transcriptional activation, and ChIP assays demonstrate co-occupancy of T/G-Mediator components at several activated genes in vivo.
SIGNOR-273175
Q9Y281
Q96S53
0
phosphorylation
down-regulates activity
0.321
Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin
SIGNOR-246711
P06213
P54646
0
phosphorylation
up-regulates
0.372
Ampk phosphorylates and activates theinsulinreceptor, providing a direct link between ampk and theinsulin pathway.
SIGNOR-195324
P22087
Q9P275
0
deubiquitination
up-regulates quantity by stabilization
0.361
USP36 deubiquitylated the nucleolar proteins nucleophosmin/B23 and fibrillarin, and stabilized them by counteracting ubiquitylation-mediated proteasomal degradation. 
SIGNOR-272291
Q13561
O43264
0
relocalization
up-regulates activity
0.685
ZW10 interacts with dynamitin, a subunit of the dynein-dynactin complex (Echeverri et al., 1996), thereby recruiting this motor to kinetochores
SIGNOR-265016
P60484
Q14653
1
dephosphorylation
up-regulates activity
0.256
PTEN can dephosphorylate IRF-3 S97 residue and facilitate its nuclear import for the IFN signaling pathway (7).|PTEN expression directly increases activated IRF-3 nuclear import and subsequent interferon (IFN) synthesis.
SIGNOR-277025
P31749
Q6PIY7
1
phosphorylation
down-regulates activity
0.2
We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition.
SIGNOR-259405
Q16778
Q68DK7
0
monoubiquitination
down-regulates activity
0.2
MSL1/2 ubiquitylates histone H2B on K 34. Importantly, only mono-ubiquitylation of H2B by MSL1/2 was detected in cells (data not shown), suggesting that MSL1/2, like RNF20/RNF40, was mainly a mono-ubiquitylase under physiological conditions.the MOF-MSL complex functions to promote both H4 K16ac and H2B K34ub. H2B K34ub, in turn, promotes H2B K120ub, H3 K4me3 and K79me2 to facilitate transcription elongation.
SIGNOR-271977
Q13315
Q969R5
1
phosphorylation
up-regulates activity
0.2
L3MBTL2 links RNF8 and RNF168 in the DNA double strand break response. The protein kinase ATM phosphorylates L3MBTL2, which recruits it to the DNA lesion by promoting the interaction between MDC1 and L3MBTL2. L3MBTL2 is subsequently ubiquitinated by RNF8, which acts as a docking site for RNF168, thereby recruiting the ubiquitin ligase to the damage site. RNF168, in turn, ubiquitinates H2A-type histones to amplify the DNA damage response and recruit downstream DNA repair proteins for proper DSB signaling.
SIGNOR-266785
P17612
P04626
1
phosphorylation
up-regulates
0.405
Pka directly phosphorylated erbb2 on thr-686, a highly conserved intracellular regulatory site that was required for the pka-mediated synergistic enhancement of neuregulin-induced erbb2-erbb3 activation and proliferation in scs.
SIGNOR-181191
Q9Y2X7
P62330
1
guanine nucleotide exchange factor
up-regulates activity
0.714
Activated RAC1 interacts with GIT1, a GAP protein of ARF6, and causes the inactivation of ARF6 [78]. As ARF6 plays a role in the promotion of the recycling of macropinosomes to the plasma membrane, the inactivation of ARF6 by RAC1 reduces the recycling of macropinosomes.
SIGNOR-277784
P19525
P16333
1
phosphorylation
down-regulates activity
0.2
In these assays, we observed that GST\u2013Nck-1 was clearly phosphorylated by GST\u2013PKR while GST was not ( Fig. 4 , upper panels).
SIGNOR-279039
Q6P1J9
Q06124
0
dephosphorylation
up-regulates activity
0.494
We found in this work that SHP2 dephosphorylates parafibromin and Cdc73, a component of the nuclear RNA polymerase II associated factor (PAF) complex, which can function as a tumor suppressor or oncoprotein in a context dependent manner.
SIGNOR-277036
Q8NBF1
P41221
1
transcriptional regulation
up-regulates quantity by expression
0.248
GLIS1, a novel hypoxia-inducible transcription factor, promotes breast cancer cell motility via activation of WNT5A
SIGNOR-269040
P51812
O15530
0
phosphorylation
up-regulates
0.655
We characterize two monoclonal antibodies raised against phosphorylated forms of the n- and c-terminal domain of rsk2 (p-s227 and p-t577, respectively). Using these two antibodies, we show that stress signals, such as uv light, induce phosphorylation and activation of the three rsks.
SIGNOR-70612
P17612
Q93034
1
phosphorylation
up-regulates activity
0.322
Elimination of the S730 but not the T325 PKA phosphorylation site of VACM-1 resulted in a complete inhibition of the VACM-1 activity, thus suggesting a direct effect of PKA on the VACM-1 receptor.
SIGNOR-250352
Q13153
O14950
1
phosphorylation
up-regulates activity
0.484
It has been shown that PAK1 phosphorylates and activates MLC2, leading to cell motility [ xref ].
SIGNOR-280053
P07948
P78527
1
phosphorylation
down-regulates activity
0.466
The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA.|We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro.
SIGNOR-279061
Q99504
P16104
1
dephosphorylation
down-regulates
0.2
Tyr142 is dephosphorylated by the tyr phosphatases eya1 and eya3.
SIGNOR-168927
P63000
O15013
0
guanine nucleotide exchange factor
up-regulates activity
0.442
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260536
Q9BZS1
P06239
0
phosphorylation
down-regulates
0.401
Lck phosphorylated tyr-342 of foxp3 by immunoprecipitation and in vitro kinase assay, and the replacement of tyr-342 with phenylalanine (y342f) abolished the ability to suppress mmp9 expression.
SIGNOR-203089
P09874
Q9H0A0
0
acetylation
up-regulates quantity by stabilization
0.2
MORC2 directly interacts with PARP1. MORC2 mediates the interaction between PARP1 and NAT10 and thereby promotes NAT10-mediated PARP1 acetylation at K949, which blocks CHFR-mediated ubiquitination and degradation of PARP1.
SIGNOR-273715
P60953
Q96HP0
0
guanine nucleotide exchange factor
up-regulates activity
0.677
Dock6 is a guanine nucleotide exchange factor (GEF) that activates the Rho family guanosine triphosphatases Rac1 and Cdc42 to regulate the actin cytoskeleton.
SIGNOR-275671
Q13627
Q12778
1
phosphorylation
down-regulates
0.506
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity.
SIGNOR-183670
P78362
P48729
0
phosphorylation
up-regulates activity
0.25
 Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins.
SIGNOR-275460
Q07002
P17612
0
phosphorylation
up-regulates activity
0.225
We previously revealed that PCTK3 is activated by two pathways: interaction with cytoplasmic cyclin A and phosphorylation at Ser-12 by protein kinase A (PKA)12. Activated PCTK3 phosphorylates retinoblastoma protein (Rb) in vitro. 
SIGNOR-264560
Q96N96
P60953
1
guanine nucleotide exchange factor
up-regulates activity
0.718
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260576
P35568
P45984
0
phosphorylation
down-regulates
0.706
Map kinases and mtor mediate insulin-induced phosphorylation ofinsulinreceptor substrate-1 on serine residues 307, 612 and 632
SIGNOR-118877
Q04637
P17252
0
phosphorylation
up-regulates activity
0.258
Phospho-proteomic and mutational analyses revealed that eIF4G1 is a substrate for PKCα at Ser1186. 
SIGNOR-276327
P48735
Q13309
0
ubiquitination
down-regulates quantity by destabilization
0.2
During the cell cycle S phase, Cyclin A-CDK2 phosphorylates IDH1 on its Threonine 157 residue (Threonine 197 in IDH2) to facilitate its recognition and ubiquitination by Skp2 E3 ubiquitin, followed by degradation through 26S proteasome
SIGNOR-267626
P06241
P43146
1
phosphorylation
up-regulates activity
0.572
Fyn tyrosine kinase, but not Src, regulates the phosphorylation of DCC in N1E-115 neuroblastoma cells.Both DCC phosphorylation and Netrin-1-induced axon outgrowth are impaired in Fyn(-/-) CN and spinal cord explants. We propose that DCC is regulated by tyrosine phosphorylation and that Fyn is essential for the response of axons to Netrin-1. these results show that DCC is phosphorylated by Fyn, but not Src, in N1E-115 cells, and that tyrosines 1261 and 1418 are the major phosphorylation sites of Fyn in vivo.
SIGNOR-268176
P16220
P17612
0
phosphorylation
up-regulates activity
0.581
Using a combination of in vitro explant assays, mutant analysis and gene delivery into mouse embryos cultured ex vivo, we demonstrate that adenylyl cyclase signalling via PKA and its target transcription factor CREB are required for WNT-directed myogenic gene expression.
SIGNOR-131307
P68400
P12821
1
phosphorylation
up-regulates activity
0.303
CK2 coprecipitated with ACE from endothelial cells, and CK2 phosphorylated both ACE and a peptide corresponding to the cytoplasmic tail. Mutation of serine(1270) within the CK2 consensus sequence almost abolished ACE phosphorylation.|These results indicate that the CK2-mediated phosphorylation of ACE regulates its retention in the plasma membrane and may determine plasma ACE levels.
SIGNOR-264425
Q92974
O96013
0
phosphorylation
down-regulates activity
0.518
PAK4 specifically phosphorylates GefH1, and this is thought to inhibit its ability to activate Rho, consequently inhibiting stress fiber formation.
SIGNOR-279245
Q9Y4K3
P01106
1
ubiquitination
down-regulates activity
0.344
We posited that TRAF6 ubiquitination of MYC at K148 prevents its acetylation, which results in diminished MYC activity ( xref ).
SIGNOR-278563
Q8WYL5
Q9BR76
1
dephosphorylation
up-regulates
0.446
Coronin 1b inhibits filament nucleation by arp2/3 complex and this inhibition is attenuated by phosphorylation of coronin 1b at serine 2, a site targeted by ssh1l.
SIGNOR-153604
O75581
Q9ULT6
0
ubiquitination
down-regulates quantity
0.656
Here we show that the cell-surface transmembrane E3 ubiquitin ligase zinc and ring finger 3 (ZNRF3) and its homologue ring finger 43 (RNF43) are negative feedback regulators of Wnt signalling. ZNRF3 is associated with the Wnt receptor complex, and inhibits Wnt signalling by promoting the turnover of frizzled and LRP6.
SIGNOR-260112
P00519
P56945
1
phosphorylation
up-regulates activity
0.462
Abl silencing inhibits CAS mediated process and constriction in resistance arteries.|CAS phosphorylation was catalyzed by Abl in an in vitro study.
SIGNOR-279671
P29323
O43795
1
phosphorylation
up-regulates activity
0.2
EphB2 kinase activity is required for Myo1b-EphB2 interaction and induced Myo1b phosphorylation.
SIGNOR-279171
Q9UM11
P24941
0
phosphorylation
down-regulates activity
0.745
 A nuclear localization signal conserved in various species was identified in CDH1, and it sufficiently targets green fluorescent protein to the nucleus. Interestingly, a CDH1-4D mutant mimicking the hyperphosphorylated form was constitutively found in the cytoplasm. In further support of the notion that phosphorylation inhibits nuclear import, the nuclear localization signal of CDH1 with two phospho-accepting serine/threonine residues changed into aspartates was unable to drive heterologous protein into the nucleus. 
SIGNOR-250732
Q14103
P17612
0
phosphorylation
up-regulates
0.349
Protein kinase a enhances, whereas glycogen synthase kinase-3 beta inhibits, the activity of the exon 2-encoded transactivator domain of heterogeneous nuclear ribonucleoprotein d in a hierarchical fashion.
SIGNOR-116144
Q14694
Q13131
0
phosphorylation
up-regulates activity
0.309
Under energy stress, USP10 activity in turn is enhanced through AMPK-mediated phosphorylation of Ser76 of USP10. 
SIGNOR-277207
Q92949
P41208
1
transcriptional regulation
up-regulates quantity by expression
0.353
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-266930
Q02535
O00712
0
transcriptional regulation
down-regulates quantity
0.25
By integrating transcriptomic profiling (RNA-seq) of Nfia- and Nfix-deficient GNPs with epigenomic profiling (ChIP-seq against NFIA, NFIB and NFIX, and DNase I hypersensitivity assays), we reveal that these transcription factors share a large set of potential transcriptional targets, suggestive of complementary roles for these NFI family members in promoting neural development
SIGNOR-268879
P12931
P14923
1
phosphorylation
up-regulates activity
0.668
Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcriptionFor instance, Src, which mainly phosphorylates Tyr86 in beta-catenin, modifies Tyr643 in plakoglobin, decreasing the interaction with E-cadherin and alpha-catenin and increasing the interaction with the alpha-catenin-equivalent protein in desmosomes, desmoplakin.
SIGNOR-247310
Q9UI47
P12830
1
relocalization
up-regulates quantity
0.567
Overexpression of CTNNA3 in a CTNNA1 negative colon carcinoma cell line resulted in the reassembly of the adherens and tight junctions through the recruitment of CTNNA3 interacting partners such as E-cadherin, β-catenin, plakoglobin, and ZO-14
SIGNOR-265492
Q9UQ84
Q13315
0
phosphorylation
up-regulates
0.83
The phosphorylation of exo1 by atm appears to regulate the activity of exo1 following resection, allowing optimal rad51 loading and the completion of hr repair.
SIGNOR-162304
P01266
Q06710
0
transcriptional regulation
up-regulates quantity by expression
0.458
The transcription factor Pax8 plays an important role in the expression of the differentiated phenotype of thyroid follicular cells. It has recently been shown that Pax8 is necessary for thyroglobulin (Tg) gene expression.
SIGNOR-251998
O94992
P06493
0
phosphorylation
down-regulates activity
0.257
Given that Cdk1 phosphorylation promotes Clp1 nucleoplasmic accumulation upon genotoxic stress and Cdk1 phosphorylation inhibits Clp1 activity, Clp1 may be only primed by its nucleolar release but not actually active under these circumstances.|In addition, Cdk1 directly phosphorylates Clp1 on TP sites primarily in early mitosis and inhibits Clp1 catalytic activity.
SIGNOR-279508
Q9UKW4
P61586
1
guanine nucleotide exchange factor
up-regulates activity
0.711
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260584
P12931
Q00610
1
phosphorylation
up-regulates
0.406
Egf-mediated clathrin phosphorylation is followed by clathrin redistribution to the cell periphery and is the product of downstream activation of src kinase by egf receptor (egfr) signaling
SIGNOR-65714
Q14680
Q15910
1
phosphorylation
up-regulates quantity by stabilization
0.329
We observed a MELK-mediated increase of EZH2 S220 phosphorylation along with a concomitant loss of EZH2 K222 ubiquitination, suggesting a phosphorylation-dependent regulation of EZH2 ubiquitination. 
SIGNOR-277480
P31751
P04049
1
phosphorylation
down-regulates activity
0.451
Akt (protein kinase b), a member of a different signaling pathway that also regulates these responses, interacted with raf and phosphorylated this protein at a highly conserved serine residue in its regulatory domain in vivo. This phosphorylation of raf by akt inhibited activation of the raf-mek-erk signaling pathway and shifted the cellular response in a human breast cancer cell line from cell cycle arrest to proliferation.
SIGNOR-235678
P49841
Q04721
1
phosphorylation
down-regulates activity
0.481
We show that gsk-3beta directly binds at c-terminal of the notch2 ankyrin repeats and phosphorylates thr-2068 and/or ser-2070, thr-2074, and thr-2093.
SIGNOR-101570
P49841
O00429
1
phosphorylation
up-regulates activity
0.388
 We identified glycogen synthase kinase (GSK)3β-dependent Drp1 phosphorylation at Ser(40) and Ser(44), which increases Drp1 GTPase activity and its mitochondrial distribution and could induce mitochondrial fragmentation.
SIGNOR-276849
P69891
Q9H165
0
transcriptional regulation
down-regulates quantity by repression
0.446
Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching.
SIGNOR-269067
P36956
Q8WU17
0
ubiquitination
down-regulates quantity
0.298
Induction of TRC8 destabilized the precursor forms of the transcription factors SREBP-1 and SREBP-2. TRC8 destablizes SREBP precursors in a RING and proteasome-dependent manner 
SIGNOR-271957
P0DPH7
Q5SQI0
0
acetylation
up-regulates quantity by stabilization
0.242
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 has been identified as an important conserved site of microtubule acetylation (6–8). This modification is considered a hallmark of stable, long-lived microtubules
SIGNOR-272244
Q14103
P49841
0
phosphorylation
down-regulates activity
0.346
In kinase assays pka phosphorylated ser-87 of hnrnp d, whereas glycogen synthase kinase-3 beta (gsk-3 beta) phosphorylated ser-83, but only if ser-87 had been pre-phosphorylated by pka. Phosphorylation of ser-87 enhanced, whereas phosphorylation of ser-83 repressed, transactivation.
SIGNOR-102582
Q9H0H5
P67775
0
dephosphorylation
down-regulates
0.303
We report here that (i) mgcracgap is phosphorylated by aurora b and cdk1, (ii) pp2a dephosphorylates aurora b and cdk1 phosphorylated sites and (iii) inhibition of pp2a abrogates mgcracgap/ect2 interaction. Therefore, pp2a may regulate cytokinesis by dephosphorylating mgcracgap and its interacting partners.
SIGNOR-160398
P18031
P08069
1
dephosphorylation
down-regulates activity
0.861
Ptp-1b can regulate igf-ir kinase activity and function and that loss of ptp-1b can enhance igf-i-mediated cell survival, growth, and motility in transformed cells.
SIGNOR-115709
P46531
Q969H0
0
ubiquitination
down-regulates quantity by destabilization
0.613
Purified recombinant cycc:cdk8 phosphorylates the notch icd within the tad and pest domains, and expression of cycc:cdk8 strongly enhances notch icd hyperphosphorylation and pest-dependent degradation by the fbw7/sel10 ubiquitin ligase in vivo.
SIGNOR-130706
Q13627
A8MYZ6
1
phosphorylation
down-regulates
0.305
Additionally, ck1, dyrk1a, and cdk2 also phosphorylate foxos at various sites to inhibit foxos activity
SIGNOR-183680
P05112
P35354
0
null
up-regulates
0.444
Cox2 Is a Direct Srf Target Gene and Controls Il4 Expression
SIGNOR-255967
Q13459
P60953
1
gtpase-activating protein
down-regulates activity
0.562
We therefore developed a screening-compatible live-cell imaging assay, using FRET-based biosensors for the prototype GTPases RHOA, RAC1 and CDC4215,19,20 (Extended Data Fig. 2 and Supplementary Note 1)|We found catalytic activities for 45/75 RhoGEFs and 48/63 RhoGAPs| Our data thus not only reveal extensive promiscuity among regulators, but also that the inactivating RhoGAPs are less selective than the activating RhoGEFs (p-value=0.02)(Supplementary Table 2).
SIGNOR-260511
Q53EL6
P23443
0
phosphorylation
down-regulates
0.614
Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.
SIGNOR-150144
P12931
P15498
1
phosphorylation
up-regulates activity
0.368
These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).
SIGNOR-279124
P29474
Q9Y243
0
phosphorylation
up-regulates activity
0.485
The phosphorylation of both S617 and S635 have also been shown to promote increased eNOS-derived NO release (Michell et al., 2002). The phosphorylaiton of S617 can be induced by PKA or Akt activity, and may serve to sensitize eNOS to calmodulin binding and modulate the phosphorylation of other eNOS sites
SIGNOR-251626
P49840
P51812
0
phosphorylation
down-regulates activity
0.265
P90-rsk and akt may promote rapid phosphorylation/inactivation of glycogen synthase kinase 3 in chemoattractant-stimulated neutrophils. These reactions were monitored with a phosphospecific antibody that only recognized the alpha- or beta-isoforms of GSK-3 when these proteins were phosphorylated on serine residues 21 and 9, respectively.
SIGNOR-110827
Q15139
P23528
1
phosphorylation
down-regulates activity
0.334
PKD1 regulates cofilin S3-phosphorylation|Both, oxidative stress as well as RhoA activation enhanced cofilin phosphorylation at S3, implicating an increased inhibition due to PKD1-mediated signalling events
SIGNOR-275944
P36507
P15056
0
phosphorylation
up-regulates
0.75
We show that, consequently, b-raf interacts with mek-1 and mek-2 with a better affinity than does c-raf-1, thus strengthening the notion that b-raf is a stronger mek activator than c-raf-l.
SIGNOR-42664