IdA
string | IdB
string | labels
int64 | mechanism
string | effect
string | score
float64 | sentence
string | signor_id
string |
|---|---|---|---|---|---|---|---|
Q9UQL6
|
P17252
| 0
|
phosphorylation
|
down-regulates activity
| 0.2
|
We also demonstrate that protein kinase D (PKD), a downstream effector of PKC, directly phosphorylates HDAC5 and stimulates its nuclear export. | Finally, we assessed the ability of PKD to phosphorylate HDAC5 in cells by employing an antibody that specifically recognizes HDAC5 that has been phosphorylated at serine 259. HDAC5 was basally phosphorylated at serine 259, and phosphorylation at this site was dramatically increased by coexpression of constitutively active PKD S/E
|
SIGNOR-249269
|
O75348
|
P0C6X7-PRO_0000037312
| 0
|
cleavage
|
down-regulates activity
| 0.2
|
Cleavage of the V-ATPase G1 fusion protein by SARS-CoV 3CLpro was found in this study (Fig. 3), implying that 3CLpro potentially cleaves the cellular V-ATPase G1, and affects the function of vacuolar H(+)-ATPase. Meanwhile, a significant intracellular acidification has been demonstrated in the 3CLpro-expressing cells (Fig. 4D). The result correlated well with previous reports in that V-ATPase-specific inhibitors cause acidic pHi [28], [29], and influences cell apoptosis
|
SIGNOR-260264
|
Q16778
|
Q14493
| 0
|
translation regulation
|
up-regulates quantity by expression
| 0.2
|
Synthesis of mature histone mRNA requires only a single processing reaction: an endonucleolytic cleavage between a conserved stem-loop and a purine-rich downstream element to form the 3' end. The stem-loop binding protein (SLBP) is required for processing, and following processing, histone mRNA is transported to the cytoplasm, where SLBP participates in translation of the histone mRNA|We used radiolabeled probes generated by PCR targeting the open reading frame (ORF) to detect histones H2A, H2B, H3, H4, and H1 and used 7SK snRNA as a loading control (Fig. 2A). The abundance of histone H2A, H2B, H3, and H4 mRNAs is reduced to 37% to 70% of control levels in the SLBP knockdown cells when compared to the C2 control.
|
SIGNOR-265386
|
P56270
|
P68400
| 0
|
phosphorylation
|
up-regulates
| 0.447
|
Site-specific mutagenesis of maz revealed that the serine residue at position 480 was the major site of phosphorylation by ckii both in vitro and in vivo. Phosphorylation of maz by ckii at this serine residue was required for maximum binding of maz to the pyrimidine-rich dna of the nuclease-hypersensitive element (nhe) in the 5'-end promoter region of the c-myc gene. Mutation of serine at position 480 to alanine eliminated the dna-binding activity of maz to this element.
|
SIGNOR-70082
|
O96013
|
P16949
| 1
|
phosphorylation
|
down-regulates activity
| 0.283
|
Indeed, we show here that inactivating phosphorylation of the endogenous stathmin on serine-16 is also induced by the active PAK4 in mitotic egg extract and is likely to participate in the observed stabilization of the MT asters ( xref , right).
|
SIGNOR-280058
|
O00257
|
Q9UNE7
| 0
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.2
|
The phosphorylation of CBX4 at T437 by casein kinase 1α (CK1α) facilitated its ubiquitination at both K178 and K280 and subsequent degradation by CHIP, and this phosphorylation of CBX4 could be reduced by TNFα.
|
SIGNOR-277513
|
P31749
|
Q5XUX0
| 1
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.2
|
Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT.
|
SIGNOR-277376
|
P49841
|
Q96R06
| 1
|
phosphorylation
|
up-regulates
| 0.271
|
Astrin acts as a substrate for gsk3beta and is phosphorylated at thr-111, thr-937 ((s/t)p motif) and ser-974/thr-978 ((s/t)xxx(s/t)-p motif;p is a phosphorylatable residue). Inhibition of gsk3beta impairs spindle and kinetochore accumulation of astrin and spindle formation at mitosis, suggesting that astrin association with the spindle microtubule and kinetochore may be dependent on phosphorylation by gsk3beta
|
SIGNOR-159578
|
Q6JBY9
|
O15264
| 0
|
phosphorylation
|
down-regulates activity
| 0.419
|
CapZIP was also phosphorylated rapidly by SAPK3/p38γ and SAPK4/p38δ, and even faster and more extensively by JNK1α1, these protein kinases phosphorylating CapZIP in vitro to >3, approx. 2 and >5 mol of phosphate/mol of protein respectively within a few minutes. Following tryptic digestion and C18 chromatography, further sites phosphorylated by JNK1α1 were identified as Ser-68, Ser-83 and Ser-216 (results not shown), and are highlighted in Figure 3.Using this antibody, we showed by immunoblotting that bacterially expressed CapZIP was phosphorylated at Ser-108 by SAPK4/p38δ, JNK1α1 and ERK2 in vitro, as well as by SAPK3/p38γ (results not shown).An important clue to the function of CapZIP and its phosphorylation came from the finding that it binds to the actin-capping protein CapZ (Figure 7A), and that cellular stresses trigger the dissociation of these two proteins (Figure 7B).Such an effect is presumably lost when CapZIP is phosphorylated and dissociates from CapZ.
|
SIGNOR-263084
|
Q9BYP7
|
Q9Y666
| 1
|
phosphorylation
|
down-regulates activity
| 0.451
|
We have shown that with-no-lysine kinase 3 (WNK3) possesses several properties that suggest it could be the Cl−/volume-sensitive regulatory kinase that, in association with protein phosphatases, reciprocally modifies the phosphorylation/dephosphorylation states of the SLC12 proteins and thus their activities|WNK3 activates NKCC1/2 and NCC and inhibits the KCCs
|
SIGNOR-264630
|
P17612
|
O43665
| 1
|
phosphorylation
|
down-regulates activity
| 0.334
|
We report in this study the acute functional regulation of rgs10 thru the specific and inducible phosphorylation of rgs10 protein at serine 168 by camp-dependent kinase a. This phosphorylation nullifies the rgs10 activity at the plasma membrane, which controls the g protein-dependent activation of the inwardly rectifying potassium channel.
|
SIGNOR-109173
|
P60953
|
Q13459
| 0
|
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
|
Q9UKV8
|
P00533
| 0
|
phosphorylation
|
up-regulates activity
| 0.534
|
Furthermore, AGO2 function is directly modulated by EGFR signaling in ERalpha negative breast cancer under states of hypoxic stress.|Here, EGFR can directly bind and phosphorylate residue Y393 of AGO2[ xref ].
|
SIGNOR-278931
|
Q9UGL1
|
Q99814
| 0
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.283
|
To this end, we confirm that KDM3A, KDM4B, KDM4C, KDM5B, KDM5C, and KDM62 are direct targets of HIF-1a while extent the list of known targets to KDM2A, KDM2B, KDM4D, KDM5A, and KDM6A. The results demonstrated that majority of the KDMs were similarly induced (KDM2A, KDM2B, KDM3A, KDM4B, KDM4C, KDM4D, KDM5A, KDM5B, KDM5C, KDM6B, and KDM7A) or repressed (KDM NO66 and KDM1A) by both HIF-1a and HIF-2a.
|
SIGNOR-271578
|
P06241
|
Q13094
| 1
|
phosphorylation
|
down-regulates
| 0.755
|
P59fyn_phosphorylated slp-76 at intermediate levels but, significantly, this phosphorylation failed to induce vav?SLP-76 complex formation
|
SIGNOR-46851
|
Q9UJM3
|
O14757
| 0
|
phosphorylation
|
down-regulates activity
| 0.326
|
Our results suggest that Chk1 phosphorylates Mig-6 on Ser 251, resulting in the inhibition of Mig-6, and that Chk1 acts as a positive regulator of EGF signalling. This is a novel function of Chk1.
|
SIGNOR-276411
|
Q06609
|
Q6PCD5
| 0
|
ubiquitination
|
up-regulates activity
| 0.401
|
Rad51 directly interacts with the N-terminal of RFWD3 and is ubiquitinated by RFWD3.
|
SIGNOR-278543
|
P49792
|
P46527
| 1
|
relocalization
|
down-regulates quantity
| 0.2
|
RanBP2 can increase the sumoylation of p27kip1. In our study, the target protein p27kip1 mainly acts as a tumor-suppressor gene in the nucleus, RanBP2 and SUMO1 act as oncogenes by promoting the nuclear-cytoplasmic translocation and debilitate the G1-arrest brought by p27kip1 accumulation in the nucleus.
|
SIGNOR-259115
|
P06493
|
P63279
| 1
|
phosphorylation
|
up-regulates activity
| 0.512
|
Overall, these results suggest that Cdk1 and cyclin B mediates the phosphorylation of Ubc9 at serine 71.
|
SIGNOR-278174
|
Q07812
|
Q9BXH1
| 0
|
relocalization
|
up-regulates
| 0.49
|
Puma promotes bax translocation by both by directly interacting with bax and by competitive binding to bcl-x(l) in uv-induced apoptosis.
|
SIGNOR-185671
|
P53350
|
Q13188
| 1
|
phosphorylation
|
down-regulates activity
| 0.331
|
We conclude that TRIM69A promotes multi-site phosphorylation of MST2.We demonstrate that TRIM69 stimulates formation of an MST2-PLK1 complex and promotes phosphorylation of MST2 at S15, a known PLK1 site. PLK1-mediated MST2 phosphorylation at S15 is necessary for subsequent phosphorylation of NEK2A to dissociate c-NAP1 from daughter centrioles (7). Thus, we provide a new molecular mechanism by which TRIM69 promotes MST2- and PLK1-mediated centrosome disjunction.
|
SIGNOR-277904
|
Q96J02
|
Q13315
| 0
|
phosphorylation
|
up-regulates activity
| 0.264
|
Here we uncover ATM as a novel positive modulator of ITCH E3-ubiquitin ligase activity. A single residue on ITCH protein, S161, which is part of an ATM SQ consensus motif, is required for ATM-dependent activation of ITCH.
|
SIGNOR-276488
|
Q9NR19
|
O15297
| 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-276560
|
P03372
|
P31751
| 0
|
phosphorylation
|
up-regulates activity
| 0.509
|
AKT activate ERalpha in the absence of estrogen. The consensus AKT phosphorylation site Ser-167 of ERalpha is required for phosphorylation and activation by AKT.
|
SIGNOR-251490
|
P53350
|
P30291
| 1
|
phosphorylation
|
down-regulates quantity by destabilization
| 0.642
|
In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.
|
SIGNOR-276040
|
P38398
|
P11387
| 1
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.463
|
Here, we show that the Ku70/Ku80 heterodimer binds with topoI, and that the DNA-dependent protein kinase (DNA-PKcs) phosphorylates topoI on serine 10 (topoI-pS10), which is subsequently ubiquitinated by BRCA1. Taken together, we conclude that BRCA1 is the E3 ligase for topoI, and the rate of topoI proteasomal degradation determines CPT response.
|
SIGNOR-277353
|
P42226
|
Q9UHD2
| 0
|
phosphorylation
|
up-regulates
| 0.674
|
We now show that stat6 is required for innate immune signaling in response to virus infection. Viruses or cytoplasmic nucleic acids trigger sting (also named mita/eris) to recruit stat6 to the endoplasmic reticulum, leading to stat6 phosphorylation on ser(407) by tbk1 and tyr(641), independent of jaks. Phosphorylated stat6 then dimerizes and translocates to the nucleus to induce specific target genes responsible for immune cell homing.
|
SIGNOR-176775
|
P35638
|
P18850
| 0
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.658
|
Apart from ER protein chaperones, ATF6 also induces the expression of CHOP and XBP1, thereby connecting the three UPR branches into an integrated signaling network
|
SIGNOR-260180
|
Q86Z02
|
Q9UER7
| 1
|
phosphorylation
|
down-regulates activity
| 0.611
|
HIPK1 phosphorylates Daxx on Ser 669, and phosphorylation of this site is important in modulating the ability of Daxx to function as a transcriptional repressor. | Therefore, phosphorylation at Ser 669 by HIPK1 diminishes the ability of Daxx to repress transcription.
|
SIGNOR-260842
|
Q16539
|
P05787
| 1
|
phosphorylation
|
up-regulates
| 0.592
|
Keratin 8 (k8) serine 73 occurs within a relatively conserved type ii keratin motif ((68)nqsllspl) and becomes phosphorylated in cultured cells and organs during mitosis, cell stress, and apoptosis. Here we show that ser-73 is exclusively phosphorylated in vitro by p38 mitogen-activated protein kinase.The ser-73 --> ala-associated filament reorganization defect is rescued by a ser-73 --> asp mutation. Also, disease-causing keratin mutations can modulate keratin phosphorylation and organization, which may affect disease pathogenesis.
|
SIGNOR-114079
|
P17600
|
Q13153
| 0
|
phosphorylation
|
up-regulates activity
| 0.349
|
Synapsin I is phosphorylated at Ser603 by p21-activated kinases. the Ser603 residue must be one of the pivotal sites for the release
|
SIGNOR-250235
|
P12931
|
P16234
| 0
|
phosphorylation
|
up-regulates activity
| 0.49
|
The increased Src activity is mainly due to the phosphorylation of Tyr-419, rather than the dephosphorylation of Tyr-530 of Src protein. PDGFR, not FAK or EGFR, appears to be the upstream protein tyrosine kinase responsible for the detachment-induced Src activation in the lung tumor cells.
|
SIGNOR-247984
|
O00308
|
O15350
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.283
|
WWP2 ubiquitinates p73 and controls its protein stability. In our study, we identified WWP2, an E3 ligase, as a novel p73-associated protein that ubiquitinates and degrades p73. In contrast, WWP2 heterodimerizes with another E3 ligase, WWP1, which specifically ubiquitinates and degrades ΔNp73.
|
SIGNOR-272233
|
Q15746
|
P17481
| 0
|
transcriptional regulation
|
down-regulates quantity by repression
| 0.2
|
Results from these experiments demonstrated that in 10T1/2 cells Hoxa10-1 increased the activity of the telokin promoter 3-fold without affecting the activity of the other promoters analyzed (Fig. 2A). Similar results were also observed in A10 SMC (data not shown). In contrast, Hoxb8 significantly repressed the activity of the telokin, smooth muscle α-actin, and SM22α promoters by 70, 50, and 70%, respectively
|
SIGNOR-261640
|
P11161
|
O00308
| 0
|
ubiquitination
|
down-regulates quantity
| 0.372
|
The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination|AIP2 interacts with and promotes ubiquitin-mediated degradation of EGR2, a zinc finger transcription factor that has been found to regulate Fas ligand (FasL) expression during activation-induced T-cell death.
|
SIGNOR-268849
|
P42768
|
Q05209
| 0
|
dephosphorylation
|
down-regulates
| 0.444
|
Furthermore, we demonstrate that pstpip serves as a scaffold protein between ptp-pest and wasp and allows ptp-pest to dephosphorylate wasp. This finding suggests a possible mechanism for ptp-pest to directly modulate actin remodeling through the pstpip-wasp interaction.
|
SIGNOR-121136
|
P49674
|
O75581
| 1
|
phosphorylation
|
up-regulates
| 0.262
|
We find that ckiepsilon binds to lrp5 and lrp6 in vitro and in vivo and identify three ckiepsilon-specific phosphorylation sites in lrp6. Two of the identified phosphorylation sites, ser1420 and ser1430, influence wnt signaling in vivo,
|
SIGNOR-145049
|
P78357
|
Q12860
| 1
|
relocalization
|
up-regulates activity
| 0.625
|
These results suggest that the targeting of contactin to different axonal domains may be determined, in part, via its association with Caspr.
|
SIGNOR-269073
|
Q9UPU5
|
Q07812
| 1
|
deubiquitination
|
up-regulates quantity by stabilization
| 0.2
|
In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. |Knockdown of USP24 decreases Bax and p300 levels
|
SIGNOR-275606
|
Q9UQL6
|
Q13950
| 1
|
deacetylation
|
down-regulates
| 0.458
|
Hdac4 and hdac5 deacetylate runx2 and lead to a smurf-mediated degradation
|
SIGNOR-145983
|
P15056
|
P31749
| 0
|
phosphorylation
|
down-regulates activity
| 0.458
|
Akt phosphorylates both S364 and S428. Akt downregulates B-Raf activity in vivo
|
SIGNOR-251472
|
Q05655
|
O14939
| 1
|
phosphorylation
|
up-regulates
| 0.463
|
Finally, we show that thr566 of pld2 is directly phosphorylated by pkc and that pld2 mutation in this region prevents pld2 activation, pld2 translocation to the edge of lamellipodia, rac translocation, and cell spreading after integrin activation
|
SIGNOR-167577
|
P49841
|
Q01974
| 1
|
phosphorylation
|
down-regulates activity
| 0.312
|
We identify ror2 ser 864 as a critical residue phosphorylated by gsk3 and required for noncanonical receptor activation by wnt5a, analogous to the priming phosphorylation of low-density receptor-related protein 6 (lrp6) in response to wnt3a.
|
SIGNOR-169642
|
Q13535
|
P38398
| 1
|
phosphorylation
|
up-regulates activity
| 0.8
|
Brca1 is phosphorylated at ser-1423 and ser-1524 after ir and uv;however, ser-1387 is specifically phosphorylated after ir, and ser-1457 is predominantly phosphorylated after uv.atr controls brca1 phosphorylation in vivo. Taken together, our results support a model in which atm and atr act in parallel but somewhat overlapping pathways of dna damage signaling but respond primarily to different types of dna lesion.
|
SIGNOR-106432
|
P53355
|
P05067
| 1
|
phosphorylation
|
up-regulates quantity
| 0.287
|
DAPK1, but not its kinase deficient mutant (K42A), significantly increased human Aβ secretion in neuronal cell culture models. Moreover, knockdown of DAPK1 expression or inhibition of DAPK1 catalytic activity significantly decreased Aβ secretion. Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Aβ.|Furthermore, DAPK1, but not K42A, triggered Thr668 phosphorylation of APP, which may initiate and facilitate amyloidogenic APP processing leading to the generation of Abeta.
|
SIGNOR-279518
|
P28482
|
Q92974
| 1
|
phosphorylation
|
up-regulates
| 0.358
|
Importantly tnf-alpha enhanced the erk pathway-dependent phosphorylation of thr-678 of gef-h1 that was key for activation.
|
SIGNOR-184469
|
P05412
|
Q00534
| 0
|
phosphorylation
|
up-regulates quantity
| 0.423
|
CDK6 additionally induced c-Jun phosphorylation, but did not activate JNK, as determined by examining JNK phosphorylation at various time-points.|CDK6 upregulates c-Jun expression.
|
SIGNOR-280222
|
Q9UKV5
|
O95140
| 1
|
polyubiquitination
|
down-regulates quantity by destabilization
| 0.3
|
Gp78 induces ubiquitylation and proteasomal degradation of Mfn1 and Mfn2.
|
SIGNOR-272887
|
Q13546
|
Q13489
| 0
|
polyubiquitination
|
up-regulates activity
| 0.747
|
CIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4).Together, our results demonstrate that depleting cIAP1/2 inhibits RIP1-4 mediated NF-kB activation without affecting RIP auto-phosphorylation.
|
SIGNOR-272713
|
P15336
|
Q9H6S0
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.275
|
Collectively, these data show that YTHDC2 plays an important role in tumor cells growth and activation/recruitment of c-Jun and ATF-2 to the YTHDC2 promoter is necessary for the transcription of YTHDC2, and that HDAC activity is required for the efficient expression of YTHDC2 in both of hepatocyte and HCC cells.
|
SIGNOR-269001
|
Q9NZV8
|
Q8N608
| 0
|
relocalization
|
up-regulates activity
| 0.533
|
Coexpression of DPP10 changes the subcellular localization of Kv4.2 expressed in COS-7 cells by promoting surface trafficking.DPP10 accelerates Kv4.2 inactivation at high and low voltages
|
SIGNOR-269006
|
Q9UQM7
|
Q13698
| 1
|
phosphorylation
|
up-regulates activity
| 0.449
|
To identify the regulatory sites of phosphorylation under physiologically relevant conditions, Ca(V)1.1 channels were purified from skeletal muscle and sites of phosphorylation on the α1 subunit were identified by mass spectrometry. Two phosphorylation sites were identified in the proximal C-terminal domain, serine 1575 (S1575) and threonine 1579 (T1579), which are conserved in cardiac Ca(V)1.2 channels (S1700 and T1704, respectively). In vitro phosphorylation revealed that Ca(V)1.1-S1575 is a substrate for both cAMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II, whereas Ca(V)1.1-T1579 is a substrate for casein kinase 2.
|
SIGNOR-263113
|
Q8TD08
|
P05412
| 1
|
phosphorylation
|
up-regulates
| 0.428
|
Up-regulation of c-jun mrna in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-jun n-terminal kinases are required for efficient up-regulation of c-jun protein. these data suggest that erks, rather than jnks, are required for c- jun up-regulation.
|
SIGNOR-91375
|
Q9NQC7
|
Q9UQM7
| 0
|
phosphorylation
|
up-regulates activity
| 0.307
|
NMDA treatment of cultured hippocampal neurons causes recruitment of CYLD, as well as CaMKII, to the postsynaptic density (PSD), as shown by immunoelectron microscopy, […] Purified CaMKII phosphorylates CYLD on at least three residues (S-362, S-418, and S-772 on the human CYLD protein Q9NQC7-1) and promotes its deubiquitinase activity.
|
SIGNOR-266442
|
Q16790
|
P17612
| 0
|
phosphorylation
|
up-regulates
| 0.2
|
Here, we report that thr443 phosphorylation at the intracellular domain of ca ix by protein kinase a (pka) is critical for its activation in hypoxic cells, with the fullest activity of ca ix also requiring dephosphorylation of ser448.
|
SIGNOR-176973
|
Q00535
|
P62136
| 1
|
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
|
P68400
|
O15259
| 1
|
phosphorylation
|
up-regulates
| 0.2
|
Casein kinase 2 (ck2)-mediated phosphorylation of three critical serine residues within a cluster of acidic amino acids in nephrocystin mediates pacs-1 binding, and is essential for colocalization of nephrocystin with pacs-1 at the base of cilia. Inhibition of ck2 activity abrogates this interaction and results in the loss of correct nephrocystin targeting.
|
SIGNOR-142343
|
P12931
|
Q16827
| 0
|
dephosphorylation
|
down-regulates activity
| 0.422
|
SRC activation triggered by loss of PTPRO leads to c-CBL degradation.|These data corroborate that PTPRO directly dephosphorylates SRC at Y416.
|
SIGNOR-277004
|
P12931
|
P20936
| 1
|
phosphorylation
|
down-regulates
| 0.615
|
The phosphorylation of p120-gap by p60c-src inhibited its ability to stimulate the ha-ras-gtpase activity
|
SIGNOR-86008
|
O96017
|
Q9UQ84
| 1
|
phosphorylation
|
down-regulates activity
| 0.565
|
Inhibition of Exo1 activity by the DDR kinase Rad53.|Unlike Sae2/CtIP activation by CDK, Exo1 phosphorylation by Rad53 limits extended resection of ssDNA at uncapped telomeres and consequently minimizes further activation of the DDR.
|
SIGNOR-279028
|
P05186
|
P10451
| 1
|
dephosphorylation
|
down-regulates activity
| 0.442
|
This result suggests that endogenous mouse TNAP dephosphorylates OPN in osteoblasts and that overexpressed human TNAP dephosphorylates OPN, compensating for the lack of endogenous TNAP in [Col1a1-Tnap +/\u2212 ;Alpl \u2212/\u2212 ] cells.
|
SIGNOR-277045
|
P00533
|
P15311
| 1
|
phosphorylation
|
up-regulates
| 0.529
|
Ezrin was initially identified as a substrate for tyrosine phosphorylation by egfr (bretscher, 1989) and phosphorylation of residues y145 and y353 were detected to high stoichiometry after egf treatment . Phosphorylation of ezrin at y353 has been delineated to signal survival during epithelial cell differentiation via the phosphatidylinositol 3-kinase (pi3k)/akt pathway.
|
SIGNOR-133215
|
P67870
|
Q9UBF6
| 1
|
phosphorylation
|
up-regulates activity
| 0.329
|
In the present study, we show the evidence that CKBBP1 is phosphorylated on threonine residue at position 10 by CKII in vitro and in vivo. Most importantly, disruption of this phosphorylation in CKBBP1 results in accumulation of IκBα and p27Kip1 in HeLa cells and inhibits cell proliferation that appears to be linked to defects in G1/S transition.
|
SIGNOR-251081
|
Q05655
|
Q15139
| 1
|
phosphorylation
|
up-regulates
| 0.269
|
Here we show that activation of pkd in response to oxidative stress requires two sequential signaling events, i.e., phosphorylation of tyr463 by abl, which in turn promotes a second step, phosphorylation of the pkd activation loop (ser738/ser742). We show that this is mediated by pkcdelta (protein kinase cdelta)
|
SIGNOR-123453
|
Q99741
|
P24941
| 0
|
phosphorylation
|
down-regulates activity
| 0.942
|
Hscdc6 is an excellent substrate for cdk2 in vitro and is phosphorylated in vivo at three sites (ser-54, ser-74, and ser-106)|An HsCdc6A1A2A3 mutant, which mimics unphosphorylated HsCdc6, is exclusively nuclear, and its expression inhibits initiation of DNA replication. An HsCdc6E1E2E3 mutant, which mimics phosphorylated HsCdc6, is exclusively cytoplasmic and is not associated with the chromatin/nuclear matrix fraction.
|
SIGNOR-67544
|
P56270
|
P27361
| 0
|
phosphorylation
|
up-regulates
| 0.299
|
Together, these results show that activation of saf-1 in response to il-1 and -6 is mediated via map kinase-regulated phosphorylation.
|
SIGNOR-114475
|
Q07666
|
Q9ULB1
| 1
|
post transcriptional regulation
|
up-regulates activity
| 0.332
|
Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA binding protein SAM68 which associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.
|
SIGNOR-269057
|
P51668
|
P50542
| 1
|
ubiquitination
|
up-regulates activity
| 0.388
|
Here we report on the identification of the protein-ubiquitin ligases that are responsible for the ubiquitination of the peroxisomal protein import receptor Pex5. It is demonstrated that each of the three RING peroxins Pex2, Pex10, and Pex12 exhibits ubiquitin-protein isopeptide ligase activity. Our results show that Pex2 mediates the Ubc4-dependent polyubiquitination whereas Pex12 facilitates the Pex4-dependent monoubiquitination of Pex5.While polyubiquitinated Pex5 is degraded by the proteasome, monoubiquitinated Pex5 is destined for a new round of the receptor cycle.
|
SIGNOR-253022
|
P40763
|
O43683
| 0
|
phosphorylation
|
up-regulates activity
| 0.251
|
This study showed that the BUB1 kinase drives the progression and proliferation of BCa by regulating the transcriptional activation of STAT3 signaling and may be an attractive candidate for therapeutic targeting in BCa.|We further identified through a series of molecular and cell biological approaches that BUB1 interacted directly with STAT3 and mediated the phosphorylation of STAT3 at Ser727.
|
SIGNOR-280198
|
Q9NY33
|
Q14145
| 1
|
cleavage
|
down-regulates quantity by destabilization
| 0.599
|
The influence of DPP3 on the Keap1-Nrf2/ARE signal pathway suggest a direct involvement of DPP3 in the oxidative stress response [8,14,31,53,99,100]. It was shown that DPP3 competes with Nrf2 through the ETGE motif to bind to Keap1 and consequently enhances the translocation of Nrf2 to the nucleus, thereby driving the expression of an array of genes encoding antioxidative enzymes [99]. More specifically, binding of DPP3 to Keap1 releases Nrf2, and thus, prevents its degradation through the 26S proteasome
|
SIGNOR-268464
|
O00141
|
P04150
| 1
|
phosphorylation
|
up-regulates activity
| 0.46
|
SGK1 also potentiated and maintained GR activation in the presence of cortisol, and even after cortisol withdrawal, by increasing GR phosphorylation and GR nuclear translocation|Having demonstrated that SGK1 mediates the cortisol-induced increase in GR phosphorylation at the S203 and S211 phospho-sites, which enhance GR nuclear translocation, but not at the S226 site, which inhibits nuclear translocation
|
SIGNOR-251669
|
P01100
|
P26439
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.2
|
We found that both SF1 and LRH1 can transcriptionally cooperate with the AP-1 family members c-JUN and c-FOS, known to be associated with enhanced proliferation of endometrial carcinoma cells, to further enhance activation of the STAR, HSD3B2, and CYP19A1 PII promoters.
|
SIGNOR-254877
|
Q9GZM8
|
Q00535
| 0
|
phosphorylation
|
up-regulates activity
| 0.772
|
Three specific phosphorylation sites (Ser198, Thr219 and Ser231) and two weak phosphorylation sites (Ser242 and Thr245) for CDK5/p35 are located in this region of NUDEL | Each single or double mutant compromised,and the triple mutant completely eliminated, interaction with 14-3-3ε. | 14-3-3ε sustains NUDEL phosphorylation and protects it from phosphatase.e dynein motor function.
|
SIGNOR-250676
|
Q6NUN9
|
Q9UBK2
| 1
|
transcriptional regulation
|
up-regulates quantity by expression
| 0.445
|
PARIS represses the expression of the transcriptional coactivator, PGC-1α and the PGC-1α target gene, NRF-1 by binding to insulin response sequences in the PGC-1α promoter.
|
SIGNOR-277627
|
O76075
|
P42574
| 0
|
cleavage
|
up-regulates
| 0.684
|
Casp3_ cleaves the 45 kda subunit at two sites to generate an active factor that produces_ dna_ fragmentation
|
SIGNOR-47419
|
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
|
Q9BRV8
|
Q9UHD2
| 0
|
phosphorylation
|
down-regulates quantity
| 0.718
|
Mechanism of endogenous regulation of the type I interferon response by suppressor of I\u03baB kinase epsilon (SIKE), a novel substrate of TANK-binding kinase 1 (TBK1).|TBK1 phosphorylation of IRF3 and SIKE displayed negative cooperativity.
|
SIGNOR-280152
|
P17252
|
O15530
| 0
|
phosphorylation
|
up-regulates
| 0.417
|
One of the most studied events controlled by ptdins(3,4,5)p3, comprises the activation of a of agc family protein kinases, including isoforms of protein kinase b (pkb)/akt, p70 ribosomal s6 kinase (s6k), serum and glucocorticoid-induced protein kinase (sgk) and protein kinase c (pkc), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (pdk1), which phosphorylates and activates the agc kinase members regulated by pi 3-kinase. We also discuss whether inhibitors of pdk1 might have chemotherapeutic potential in the treatment of cancers in which the pdk1-regulated agc kinases are constitutively activated.
|
SIGNOR-126066
|
P35228
|
P27361
| 0
|
phosphorylation
|
up-regulates
| 0.354
|
Erk phosphorylated inos on ser745. Mutation of ser745 to ala did not affect basal inos activity but eliminated inos phosphorylation and activation in response to b1r agonist.
|
SIGNOR-157711
|
P06748
|
Q13315
| 0
|
phosphorylation
|
up-regulates activity
| 0.352
|
In addition to Serine 125, ATM may also phosphorylate other sites on NPM.
|
SIGNOR-280182
|
P06493
|
Q15717
| 1
|
phosphorylation
|
down-regulates activity
| 0.407
|
Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.
|
SIGNOR-279014
|
Q07817
|
P06493
| 0
|
phosphorylation
|
down-regulates activity
| 0.537
|
Cyclin-Dependent Kinase 1-Mediated Bcl-xL/Bcl-2 Phosphorylation Acts as a Functional Link Coupling Mitotic Arrest and Apoptosis|These findings suggest a model whereby a switch in the duration of CDK1 activation, from transient during mitosis to sustained during mitotic arrest, dramatically increases the extent of Bcl-xL/Bcl-2 phosphorylation, resulting in inactivation of their antiapoptotic function. Thus, phosphorylation of antiapoptotic Bcl-2 proteins acts as a sensor for CDK1 signal duration and as a functional link coupling mitotic arrest to apoptosis.
|
SIGNOR-267986
|
P27708
|
P23443
| 0
|
phosphorylation
|
up-regulates activity
| 0.372
|
CAD as a direct substrate of S6K1. mTORC1 signaling posttranslationally regulated this metabolic pathway via its downstream target ribosomal protein S6 kinase 1 (S6K1), which directly phosphorylates S1859 on CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase), the enzyme that catalyzes the first three steps of de novo pyrimidine synthesis. The direct regulation of CAD by S6K1 serves as a mechanism to increase the pool of nucleotides available for the RNA and DNA synthesis that accompanies cell growth.
|
SIGNOR-267443
|
Q8N3F0
|
O15111
| 0
|
phosphorylation
|
down-regulates activity
| 0.2
|
INKIT interacted with IKKα/β and TBK1/IKKɛ, impairing the recruitment and phosphorylation of p65 and IRF3. Viral infection induced IKK-mediated phosphorylation of INKIT at Ser58, resulting in its dissociation from the IKKs. Our findings thus uncover INKIT as a regulator of innate antiviral responses.
|
SIGNOR-273612
|
O95644
|
Q86V86
| 0
|
phosphorylation
|
up-regulates activity
| 0.246
|
In addition to PIM1, also PIM2 and PIM3 were able to phosphorylate WT, but not MM NFATC1 in vitro (Fig. (Fig.22c).
|
SIGNOR-276773
|
Q9GZU7
|
P84022
| 1
|
dephosphorylation
|
up-regulates activity
| 0.433
|
SCP1 Dephosphorylates Smad2/3 in the Linkers|MAPK-mediated linker phosphorylation appears to have a dual role in Smad2/3 regulation. Mitogens and hyperactive Ras result in extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Smad3 at Ser-204, Ser-208, and Thr-179 and of Smad2 at Ser-245/250/255 and Thr-220. Mutation of these sites increases the ability of Smad3 to activate target genes, suggesting that MAPK phosphorylation of Smad3 is inhibitory (11, 12). However, in contrast, ERK-dependent phosphorylation of Smad2 at Thr-8 enhances its transcriptional activity
|
SIGNOR-248792
|
P06241
|
Q9Y210
| 1
|
phosphorylation
|
up-regulates activity
| 0.505
|
Fyn phosphorylates TRPC6 and increases its diacylglycerol stimulated single channel activity.
|
SIGNOR-279717
|
Q99801
|
P19784
| 0
|
phosphorylation
|
up-regulates
| 0.315
|
In vitro kinase assays followed by mass spectrometric analyses demonstrated that ck2 phosphorylated recombinant nkx3.1 on thr89 and thr93. We have also determined that nkx3.1 is degraded primarily through a proteasomal pathway, suggesting that phosphorylation by ck2 protects nkx3.1 from degradation.
|
SIGNOR-145501
|
P21127
|
Q96I25
| 1
|
phosphorylation
|
up-regulates activity
| 0.207
|
However, Clk1 enhanced SPF45 protein expression, but not mRNA expression, whereas inhibition of Clk1 increased SPF45 degradation through a proteasome dependent pathway.|In the present work, we show that Clk1 phosphorylates SPF45 in vitro on eight serine residues, all of which are N-terminal to the RRM domain required for splicing.
|
SIGNOR-279510
|
P29474
|
P31749
| 0
|
phosphorylation
|
up-regulates
| 0.877
|
Recently many investigators have shown that protein phosphorylation of enos by several serine/threonine kinases is a critical control step for no production by endothelial cells. Phosphorylation by amp kinase, akt (or protein kinase b), or protein kinase a on serine 1179 (bovine) or serine 1177 (human) of enos leads to enhanced activity of the enzyme and, thus, augmented production of no.
|
SIGNOR-112363
|
Q13131
|
Q13586
| 1
|
phosphorylation
|
down-regulates activity
| 0.2
|
STIM1 is a novel exercise‐regulated AMPK substrate. Phosphorylation of STIM1 by AMPK suppresses SOCE
|
SIGNOR-277299
|
P10912
|
Q9HD43
| 0
|
dephosphorylation
|
down-regulates activity
| 0.295
|
Protein tyrosine phosphatases (PTPs) play key roles in switching off tyrosine phosphorylation cascades, such as initiated by cytokine receptors. We have used substrate-trapping mutants of a large set of PTPs to identify members of the PTP family that have substrate specificity for the phosphorylated human GH receptor (GHR) intracellular domain. Among 31 PTPs tested, T cell (TC)-PTP, PTP-beta, PTP1B, stomach cancer-associated PTP 1 (SAP-1), Pyst-2, Meg-2, and PTP-H1 showed specificity for phosphorylated GHR
|
SIGNOR-248802
|
Q14289
|
Q9ULH1
| 1
|
phosphorylation
|
down-regulates activity
| 0.458
|
The tyrosine kinase Pyk2 regulates Arf1 activity by phosphorylation and inhibition of the Arf-GTPase-activating protein ASAP1. Pyk2 directly phosphorylates ASAP1 on tyrosine residues in vitro and increases ASAP1 tyrosine phosphorylation when co-expressed in HEK293T cells.Phosphorylation of tyrosine 308 and 782 affects the phosphoinositide binding profile of ASAP1, and fluorimetric Arf-GTPase assays with purified proteins revealed an inhibition of ASAP1 GTPase-activating protein activity by Pyk2-mediated tyrosine phosphorylation.
|
SIGNOR-263186
|
Q05086
|
O94788
| 1
|
ubiquitination
|
down-regulates quantity by destabilization
| 0.2
|
Hyperactivity of E3 ubiquitin (Ub) ligase UBE3A, stemming from 15q11-q13 copy number variations, accounts for 1%-3% of ASD cases worldwide, but the underlying mechanisms remain incompletely characterized. Here we report that the functionality of ALDH1A2, the rate-limiting enzyme of retinoic acid (RA) synthesis, is negatively regulated by UBE3A in a ubiquitylation-dependent manner.
|
SIGNOR-265135
|
Q00534
|
Q01196
| 1
|
phosphorylation
|
up-regulates
| 0.615
|
We have identified four phosphorylation sites on aml1c that are necessary for transcriptional activity of aml1c in k562 and 293t cells (27).4 mutation of these four sites (serine 276, serine 293, serine 303, and threonine 300) to alanine abolishes transcriptional activation, whereas mutation of these sites to aspartic acid (which mimics phosphorylation) results in a hyperactive protein.
|
SIGNOR-138953
|
Q02750
|
P41279
| 0
|
phosphorylation
|
up-regulates
| 0.574
|
Activation of mek family kinases requires phosphorylation of two conserved ser/thr residues.Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human mek1 are the primary sites for phosphorylation by c-raf
|
SIGNOR-36453
|
P55211
|
P62136
| 0
|
dephosphorylation
|
up-regulates
| 0.2
|
Pp1 dephosphorylated thr125 site of caspase-9 and activated caspase-9 to mediate il-2 deprivation-induced apoptosis.
|
SIGNOR-195992
|
O75306
|
P06493
| 0
|
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 phosphorylation in each of the relevant CI subunits results in impairment of CI function.|These results were confirmed by generating phosphorylation defective forms of the five CI subunits through substitutions of S/T residues with Alanine (A) on either Cdk1 optimal or minimal consensus motifs (T383 on NDUFV1, S105 on NDUFV3, S364 on NDUFS2, S55/S29/T5 on NDUFB6, and T142/T120 on NDUFA12). The mutation of Cdk1 consensus motifs severely diminished their phosphorylation
|
SIGNOR-275592
|
Q5D1E8
|
P23769
| 1
|
post transcriptional regulation
|
up-regulates quantity
| 0.2
|
Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA
|
SIGNOR-259943
|
Q9UPN4
|
Q86YT6
| 0
|
ubiquitination
|
down-regulates
| 0.43
|
We demonstrate that the E3 ubiquitin ligase MIB1 is a new component of centriolar satellites, which interacts with and ubiquitylates AZI1 and PCM1 and suppresses primary cilium formation. Whereas these proteins are degraded prior to the ciliation process, MIB1 appears to maintain its targets in a latent state through inhibitory ubiquitylation that is reversed during ciliogenesis and in response to cell stress.The precise mechanism by which MIB1 inhibits primary cilium formation through ubiquitylation of ciliogenesis-promoting target proteins such as AZI1 and PCM1 remains to be determined.
|
SIGNOR-272876
|
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