IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
P26439
P01100
0
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
Q9Y243
Q96ST2
1
phosphorylation
up-regulates activity
0.381
The data presented in this report confirmed the differential phosphorylation of IWS1 at Ser720/Thr721 by Akt3 and Akt1 and showed that its phosphorylation at this site is required for the recruitment of SetD2 to the Spt6-IWS1-Aly/REF complex.
SIGNOR-273496
Q16539
Q14790
1
phosphorylation
down-regulates
0.55
P38-mapk can directly phosphorylate and inhibit the activities of caspase-8
SIGNOR-122103
Q8TB45
Q15418
0
phosphorylation
down-regulates
0.492
We found that deptor was rapidly phosphorylated on three serines in a conserved degron, facilitating binding and ubiquitylation by the f box protein _trcp, with consequent proteasomal degradation of deptor. Phosphorylation of the _trcp degron in deptor is executed by ck1
SIGNOR-176883
P53805
Q13627
0
phosphorylation
up-regulates
0.562
In the present study, dyrk1a is shown to directly interact with and phosphorylate rcan1 at ser112 and thr192 residues. Dyrk1a-mediated phosphorylation of rcan1 at ser112 primes the protein for the gsk3_-mediated phosphorylation of ser108.
SIGNOR-102290
P03372
P50613
0
phosphorylation
up-regulates
0.413
Activation of estrogen receptor alpha by s118 phosphorylation involves a ligand-dependent interaction with tfiih and participation of cdk7.
SIGNOR-81170
Q06413
Q16539
0
phosphorylation
up-regulates activity
0.696
We found that in monocytic cells, lps increases the transactivation activity of mef2c through p38-catalysed phosphorylation.
SIGNOR-47136
Q13444
P08631
0
phosphorylation
up-regulates
0.355
Hck, and to a lesser extent lck, phosphorylated the adam15. Deletion and point mutation analysis of the adam15 cytoplasmic domain confirmed the importance of the proline-rich motifs for grb2 and lck binding and indicated the regulatory nature of tyr(715) and tyr(735). These data demonstrate selective, phosphorylation-dependent interactions of adam15 with src family ptks and grb2, which highlight the potential for integration of adam functions and cellular signaling.
SIGNOR-112919
P29353
P06241
0
phosphorylation
up-regulates
0.732
Syk and zap-70 were able to phosphorylate the y239 and y240 sites, and less efficiently the y317 site. Of the two potential grb2 binding sites (y239 and y317), y239 appears to play a greater role in recruiting sos through grb2.
SIGNOR-59623
P30304
Q9H4B4
0
phosphorylation
down-regulates
0.383
Here, we demonstrate that glycogen synthase kinase-3beta (gsk-3beta) phosphorylates cdc25a to promote its proteolysis in early cell-cycle phases. Phosphorylation by gsk-3beta requires priming of cdc25a, and this can be catalyzed by polo-like kinase 3 (plk-3)
SIGNOR-160228
Q13464
Q9NRY4
1
phosphorylation
down-regulates activity
0.414
these results indicate that Rho-kinase can phosphorylate p190A RhoGAP at Ser1150 in COS7 cells. Similarly, the immunoblot analysis, through the use of the anti-p190A RhoGAP-pT1226 and -pS1236 antibodies, revealed that Rho-kinase can phosphorylate p190A RhoGAP at Thr1226 and Ser1236 in COS7 cells
SIGNOR-276177
P25098
P08913
1
phosphorylation
down-regulates activity
0.2
The alpha 2A-adrenergic receptor (alpha 2AAR) undergoes rapid functional desensitization caused by phosphorylation of the receptor by the beta-adrenergic receptor kinase (beta ARK). beta ARK-mediated phosphorylation of alpha 2C10 occurs at Ser-296-299 in the third intracellular loop, and this represents the critical step in rapid agonist-promoted desensitization.
SIGNOR-251440
P24941
P29350
1
phosphorylation
down-regulates quantity by destabilization
0.287
Interaction between SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated Cdk2 phosphorylated SHP-1 protein.
SIGNOR-279147
Q12972
P19784
0
phosphorylation
up-regulates activity
0.473
Phosphorylation of NIPP-1 in a heterodimeric complex with the catalytic subunit of protein phosphatase-1 resulted in an activation of the holoenzyme without a release of NIPP-1. Sequencing and phosphoamino acid analysis of tryptic phosphopeptides enabled us to identify Ser178 and Ser199 as the phosphorylation sites of protein kinase A, whereas Thr161 and Ser204 were phosphorylated by protein kinase CK2.
SIGNOR-251023
P04637
O14980
0
relocalization
down-regulates activity
0.549
We identify the major poly(ADP-ribosyl)ated sites of p53 by PARP-1 and find that PARP-1-mediated poly(ADP-ribosyl)ation blocks the interaction between p53 and the nuclear export receptor Crm1, resulting in nuclear accumulation of p53. These findings molecularly link PARP-1 and p53 in the DNA-damage response, providing the mechanism for how p53 accumulates in the nucleus in response to DNA damage.|PARP-1 is super-activated by binding to damaged DNA, and poly(ADP-ribosyl)ates p53. Poly(ADP-ribosyl)ation probably induces a structural change that mask the NES, and thus Crm1 can no longer target p53 to the nuclear export machinery, resulting in accumulation of p53 in the nucleus.
SIGNOR-260067
P49411
Q9BXM7
0
phosphorylation
down-regulates activity
0.2
PINK1 interacts with the autophagy effector TUFm and phosphorylates TUFm at Ser222. These results indicated that p222-hTUFm sequestered more monomer Atg5 and reduced the conjugated Atg5-Atg12 complex to subdue mitophagy.
SIGNOR-266382
Q16665
P01584
1
transcriptional regulation
up-regulates quantity by expression
0.336
We finally confirmed that in the absence of HIF-1α there was a significant reduction at the protein level in pro-caspase-1, activated caspase-1, pro-IL-1β, and ultimately active IL-1β (Fig. 4g and h). These data show that adenosine induced up-regulation of IL-1β is dependent on a CREB/HIF-1α pathway which is distinct from the NF-kB pathway used for initial production of IL-1β in response to LPS.
SIGNOR-251718
Q16827
P40763
1
dephosphorylation
down-regulates activity
0.376
In addition, this group found that PTPRO dephosphorylated STAT3 at Y705 and S727 then attenuated STAT3 signalling.
SIGNOR-277062
P61586
O15013
0
guanine nucleotide exchange factor
up-regulates activity
0.525
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-260535
Q9Y484
Q9H093
0
phosphorylation
up-regulates activity
0.262
WIPI4 is stimulated by AMPK, NUAK2 and BRSK2. This finding is supported by the results of our kinome screening, which identified AMPK and the AMKP-related kinases NUAK2 and BRSK2, all of which function downstream of LKB1 (ref. 69) and stimulate the localization of WIPI4 to nascent autophagosomes.
SIGNOR-268481
O00548
Q86YT6
0
ubiquitination
up-regulates activity
0.743
Mib physically interacts with Delta and promotes its ubiquitination and internalization [66], which have been shown to up-regulate Notch activity.
SIGNOR-209750
P48200
P40337
0
ubiquitination
down-regulates quantity by destabilization
0.359
We show here that IRP2 can interact with pVHL in co-transfection/co-immunoprecipitation assays. Furthermore, pVHL is able to promote the ubiquitination and the decay of transfected IRP2.
SIGNOR-271421
Q13464
Q6WCQ1
1
phosphorylation
down-regulates
0.296
Enhanced rho kinase activity induces endothelial barrier dysfunction by a contractile mechanism via inactivation of myosin phosphatase (mp)..
SIGNOR-157593
Q9UKB1
Q9HAW4
1
ubiquitination
down-regulates
0.345
Claspin degradation was triggered by its interaction with, and ubiquitylation by, the scfbetatrcp ubiquitin ligase.
SIGNOR-148438
P10415
Q92934
0
relocalization
down-regulates activity
0.801
Apoptosis is initiated when Bcl-2 and its prosurvival relatives are engaged by proapoptotic BH3-only proteins via interaction of its BH3 domain with a groove on the Bcl-2-like proteins. These interactions have been considered promiscuous, but our analysis of the affinity of eight BH3 peptides for five Bcl-2-like proteins has revealed that the interactions vary over 10,000-fold in affinity, and accordingly, only certain protein pairs associate inside cells. Bim and Puma potently engaged all the prosurvival proteins comparably. Bad, however, bound tightly to Bcl-2, Bcl-xL, and Bcl-w but only weakly to A1 and not to Mcl-1.
SIGNOR-133756
O15492
P07948
0
phosphorylation
up-regulates activity
0.346
Lyn kinase phosphorylated recombinant RGS16 in vitro. Induction of RGS16 tyrosine phosphorylation was associated with increased RGS16 protein levels and enhanced GAP activity in cell membranes.
SIGNOR-251410
Q99640
P53350
0
phosphorylation
down-regulates activity
0.721
Here, we have shown that Plk1 is responsible for part of the phosphorylation of Myt1 during M phase. The kinase activity of human Myt1 is reported to be decreased during M phase, and the decreased activity correlates with hyperphosphorylated forms of Myt1 (35, 37). We then tested the ability of these mutant forms of Myt1 (GST fusion proteins), to serve as a substrate for Plk1 in vitro. Quantification of the result (Fig. 5C) showed that Ser-426 is the major phosphorylation site by Plk1 in vitro and Thr-495 the second major site.
SIGNOR-263096
Q8IWJ2
P20645
1
relocalization
up-regulates activity
0.532
Rab9-dependent transport from late endosomes to the Golgi requires the Rab9 effectors p40 (Diaz et al., 1997) and TIP47 (Diaz and Pfeffer, 1998), a protein that recognizes the cytoplasmic domains of the two types of MPRs and packages them into nascent transport vesicles (Carroll et al., 2001). MPR recycling also utilizes a TGN-localized coiled-coil protein named GCC185 that is also a Rab9 effector
SIGNOR-253086
P06493
O15151
1
phosphorylation
down-regulates
0.407
Cdc2p34 phosphorylates mdmx on ser 96 in vitro. Mutation within this site (mdmx(s96a)) impairs, whereas phosphomimic substitution (mdmx(s96d)) increases the cytoplasmic localization of mdmx, suggesting that cdk2/cdc2p34 phosphorylation is required for export of mdmx from the nucleus
SIGNOR-134388
P49593
O14757
1
dephosphorylation
down-regulates activity
0.2
As a result, inactivation of Chk1 by POPX2 leads to impaired G1S checkpoint activation and cells are able to proceed from G1 to S phase despite DNA damage.|We also determined that POPX2 can dephosphorylate Chk1Ser317 and -Ser345 and is a potential regulator of Chk1 function in the cell.
SIGNOR-276988
P17706
P23458
1
dephosphorylation
down-regulates activity
0.767
Upon ligand binding, IL-2R , IL-6R or LeptinR , IFN-_R , IFN-_R and PRLR or growth hormone (GH) receptor associated JAKs become activated. These JAKs mediate phosphorylation of specific tyrosine residues and recruit STATs. Activated STATs are released from the receptor and translocate to the nucleus. PTP1B dephosphorylates JAK2, TYK2 and STAT5 . The 45-kDa form of TC-PTP was shown to dephosphorylate JAK1 and JAK3 as well as STAT1, STAT3 and STAT5.
SIGNOR-134620
P49802
P17252
0
phosphorylation
down-regulates activity
0.364
TNF-α rapidly increases the concentration of functionally active RGS7 protein through two mechanisms. TNF-induced dephosphorylation of serine 434 liberates RGS7 from 14-3-3 binding and inhibition. , PKC α catalyzes the incorporation of phosphate into a truncation of RGS7 fused to maltose-binding protein (MBP.RGS7315–469).
SIGNOR-263165
Q9GZY6
P43405
0
phosphorylation
up-regulates activity
0.592
Our results indicated that human LAB was primarily phosphorylated on three membrane-distal tyrosines, Tyr(136), Tyr(193), and Tyr(233). Mutation of these three tyrosines abolished Grb2 binding and LAB function. Our data suggested that these tyrosines are the most important tyrosines for LAB function.The dramatic reduction in phosphorylation of the LAB Y233F mutant suggested that Tyr233 is a primary target of the Syk family kinases.
SIGNOR-273576
P06493
Q99638
1
phosphorylation
up-regulates activity
0.361
Here we present evidence that thr292 of hrad9 is subject to cdc2-dependent phosphorylation in mitosis. Furthermore, our data are also consistent with four other hrad9 phosphorylation sites (ser277, ser328, ser336, and thr355) being regulated in part by cdc2. We also identify ser387 as a novel site of hrad9 constitutive phosphorylation and show that phosphorylation at ser387 is a prerequisite for one form of dna damage-induced hyperphosphorylation of hrad9.
SIGNOR-101055
Q92824
P01178
1
cleavage
down-regulates quantity
0.248
Oxytocin-extended form is further cleaved by enzymatic activity to yield the nine-amino-acid active peptide, OT. The proteolysis may involve several pro-hormone convertases, convertase 2 (PC2) (20p11-1-11.2) and convertase 5 (PC5) (9q21.3) (Gabreels et al 1998). Both enzymes are found in OT neurosecretory vesicles and are a part of a family of subtilisen/kexinlike convertases (Seidah et al 1994). It is a product of the OT gene located at human gene locus 20p13 (Rao et al 1992). The processing cascade results in the production of neurophysin I and OT extended form (OT-X), which is OT with a C-terminal, three-amino-acid extension.
SIGNOR-270327
O94811
Q00535
0
phosphorylation
down-regulates activity
0.403
Here we show that TPPP induces tubulin self-assembly into intact frequently bundled microtubules, and that the phosphorylation of specific sites distinctly affects the function of TPPP. The phosphorylation sites Thr(14), Ser(18), Ser(160) for Cdk5; Ser(18), Ser(160) for ERK2, and Ser(32) for PKA were identified by mass spectrometry. The phosphorylation by ERK2 or Cdk5 resulted in the loss of microtubule-assembling activity of TPPP.
SIGNOR-262931
P46934
Q9BT67
0
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 function and impede the degradation of mature hERG proteins mediated by Nedd4-2.
SIGNOR-260997
P49768
Q9Y4K3
0
ubiquitination
up-regulates quantity by stabilization
0.559
We have also observed that ubiquitination of PS1 by TRAF6 increases the stability of PS1 holoprotein, and TRAF6-deficiency coincides with reduced endogenous PS1 and PS2 levels.
SIGNOR-278601
P11168
P17612
0
phosphorylation
down-regulates activity
0.309
GLUT2 is rapidly phosphorylated by protein kinase A following activation of adenylyl cyclase by forskolin. serines 489 and 501/503 and threonine 510 in the carboxyl-terminal tail of the transporter are the in vitro and in vivo sites of phosphorylation. Stimulation of GLUT2 phosphorylation in beta cells reduces the initial rate of 3-O-methyl glucose uptake by approximately 48% but does not change the Michaelis constant. a consequence of GLUT2 phosphorylation is a reduction of its catalytic activity.
SIGNOR-250050
P17612
Q07954
1
phosphorylation
up-regulates activity
0.324
LRP phosphorylation is mediated by PKA at residue serine 76 of its cytoplasmic tail and that this phosphorylation contributes to receptor-mediated endocytosis.
SIGNOR-250000
P31749
P46937
1
phosphorylation
down-regulates
0.593
One protein that associates with 14-3-3 in an akt-dependent manner is shown here to be the yes-associated protein (yap), which is phosphorylated by akt at serine 127, leading to binding to 14-3-3. Akt promotes yap localization to the cytoplasm, resulting in loss from the nucleus where it functions as a coactivator of transcription factors including p73.
SIGNOR-252593
O14733
O15264
1
phosphorylation
up-regulates activity
0.436
p38-δ is activated by environmental stress, extracellular stimulants, and MAPK kinase-3, -4, -6, and -7. we investigated whether this Thr180-Gly-Tyr182 motif was essential for p38-δ activation. Taken together, these results suggest that the dual phosphorylation TGY motif is required for p38-δ activation.
SIGNOR-273954
O95251
Q7Z6Z7
0
ubiquitination
down-regulates quantity by destabilization
0.2
Moreover, we determined that Huwe1 is a novel E3 ligase for Myst2 degradation in mESCs, and Brpf3 disturbs Huwe1 mediated ubiquitination of Myst2 via interaction with Huwe1 and Myst2.
SIGNOR-278652
P09619
P29353
1
phosphorylation
up-regulates
0.659
In this study, we have characterized the interaction between the pdgf beta-receptor and shc. multiple autophosphorylation sites in the pdgf beta-receptor are responsible for the binding of shc.
SIGNOR-36906
P11309
Q13761
1
phosphorylation
up-regulates quantity
0.353
Inhibition of Pim1 kinase prevents peanut allergy by enhancing Runx3 expression and suppressing T (H) 2 and T (H) 17 T-cell differentiation.|Pim1 kinase phosphorylates and stabilizes Runx3 and alters its subcellular localization.
SIGNOR-279547
P49841
O15379
1
phosphorylation
up-regulates activity
0.285
Given that pharmacological inhibition of GSK3beta inhibits HDAC3 neurotoxicity, we explored the possibility that HDAC3 was directly phosphorylated by GSK3beta.|HDAC3 is directly phosphorylated by GSK3\u03b2, suggesting that the neuronal death-promoting action of GSK3\u03b2 could be mediated through HDAC3 phosphorylation.
SIGNOR-278400
P78352
Q8NFZ3
0
relocalization
up-regulates activity
0.2
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264190
P03956
O00755
0
transcriptional regulation
up-regulates quantity by expression
0.261
Because MMP1 is also another direct target of the canonical Wnt pathway (22), Wnt7a overexpression upregulated MMP1/10 to degrade the extracellular matrix and to facilitate UBC cell invasion.
SIGNOR-278868
P23467
P08581
1
dephosphorylation
down-regulates
0.364
Ptp1b and shp-2 are bound to the c-met receptor to control its activity. Although the binding of ptp1b increases when there is a decrease in c-met activation and acts as a negative regulator of the receptor, the increased binding and phosphorylation of shp-2 coincide with maximal stimulation of c-met, acting as a positive regulator.
SIGNOR-139560
O94806
Q9GZY8
1
phosphorylation
up-regulates activity
0.2
The mitochondrial fission factor (MFF), the main mitochondrial receptor for the Dynamin-related protein 1 (DRP1), is directly phosphorylated by Protein Kinase D (PKD) specifically during mitosis. PKD-dependent MFF phosphorylation is required and sufficient for mitochondrial fission in mitotic but not in interphasic cells.|PKD directly phosphorylates MFF on serines 155, 172, and 275
SIGNOR-275945
Q92934
P17612
0
phosphorylation
down-regulates
0.542
Ser-155 is the major phosphoacceptor site for pka on bad, but that pka also phosphorylates ser-112 and ser-136. Phosphorylated bad appears to be the inactive moiety. These results implicate pkac as the candidate kinase for s112 phosphorylation in vivo.
SIGNOR-67387
Q15139
P35236
1
phosphorylation
up-regulates activity
0.2
HePTP is phosphorylated by PKC isozymes at Ser-225 in vitro. While all isozymes phosphorylated Ser-225 predominantly and Ser-113 to a lesser extent (Fig. ​(Fig.5),5), they differed strikingly in how much 32P they incorporated into HePTP during the 30-min assay. PKC θ was the most efficient, while PKC ζ and PKC μ were clearly less potent; PKC δ, ɛ, and η were quite inefficient.
SIGNOR-276046
O15055
P48730
0
phosphorylation
down-regulates quantity by destabilization
0.869
Human casein kinase Idelta phosphorylation of human circadian clock proteins period 1 and 2. We have now extended our previous studies to show that human casein kinase Idelta (hCKIdelta), the closest homologue to hCKIepsilon, associates with and phosphorylates hPER1 and causes protein instability. Furthermore, we observed that both hCKIdelta and hCKIepsilon phosphorylated and caused protein instability of human period 2 protein (hPER2).
SIGNOR-268000
P78352
Q8N0W4
0
relocalization
up-regulates activity
0.754
Like NRXNs, NLGNs bind to intracellular PDZ-domain proteins, but in contrast to NRXNs, NLGNs bind to class I PDZ domains such as those contained in PSD95, a postsynaptic MAGUK protein65. PSD95 and its homologues are centrally involved in recruiting glutamate receptors at postsynaptic sites66. Similarly to CASK, PSD95 binds to intracellular adaptor proteins, and especially to GKAP (a protein that binds to the guanylate-kinase domain of PSD95), which, in turn, binds to SHANK proteins (Fig. 1b). A possible role of these interactions is to recruit postsynaptic adaptor proteins to the site of synaptic junctions.
SIGNOR-264192
P06493
O14745
1
phosphorylation
down-regulates activity
0.276
During the early stages of mitosis in HeLa cells, Cdc2 phosphorylates EBP50 on serine residues 280 and 302.|Phosphorylation by Cdc2 inhibits EBP50's role in forming microvilli in interphase but not mitotic cells. (A) Results from scoring JEG-3 cells for the presence of microvilli; error bars indicate mean \u00b1 SD. (B) Representative images from the microvillar rescue assay.
SIGNOR-278305
Q02750
P55211
1
phosphorylation
down-regulates activity
0.439
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK|The opposing protein kinase activity is overcome by treatment with the broad-specificity kinase inhibitor staurosporine or with inhibitors of MEK1/2
SIGNOR-249385
Q9Y572
O43318
0
phosphorylation
up-regulates activity
0.2
Collectively, TAK1 activates RIPK3, RIPK3 activates TAK1, and RIPK1 activates RIPK3 and facilitates interaction between TAK1 and RIPK3.|We found that prolonged and hyperactivation of TAK1 induced phosphorylation and activation of RIPK3, leading to necrosis without caspase activation.
SIGNOR-279634
P23769
P15976
0
transcriptional regulation
down-regulates quantity by repression
0.443
GATA-2 induces the expression of GATA-1, which first activates its cofactor FOG-1, and then downregulates GATA-2 cooperatively with FOG-1.
SIGNOR-256060
Q9NZQ7
Q9Y2A9
0
glycosylation
up-regulates activity
0.2
These results further suggested that B3GNT3 mediates PD-L1 and PD-1 interaction through N-linked glycosylation instead of O-linked glycosylation
SIGNOR-275389
P17676
P49841
0
phosphorylation
up-regulates activity
0.457
We found that expression of srebf1a depended on GSK3β activity and that GSK3β activity was necessary for C/EBPβ phosphorylation at Thr188
SIGNOR-251644
P45983
P98177
1
phosphorylation
up-regulates
0.612
Upon treatment of cells with h2o2, the small gtpase ral is activated and this results in a jnk-dependent phosphorylation of foxo4 on threonine 447 and threonine 451. This ral-mediated, jnk-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of foxo4 after h2o2 treatment.
SIGNOR-130385
P27361
P41212
1
phosphorylation
down-regulates
0.317
Tel became phosphorylated by erk on two serine residues, ser213 and ser257, in the internal domain between the hlh and ets domains. Tel lost its abilities to repress transcription through the phosphorylation.
SIGNOR-123656
Q00987
Q9Y294
1
ubiquitination
down-regulates quantity by destabilization
0.267
We found that MDM2 overexpression also decreased the ASF1A half-life time, indicating an accelerated ASF1A degradation.|We next examined whether the presence of RAD6 is essential for MDM2-induced ASF1A ubiquitination.
SIGNOR-278822
Q92777
P17612
0
phosphorylation
down-regulates activity
0.326
Synapsin phosphorylation in the A domain, at the only phosphorylation site shared by all synapsins, dissociates synapsins from synaptic vesicles.This site is located in the N-terminal A domain and is a substrate for both PKA and CaM Kinase I
SIGNOR-250059
Q05397
Q9NZN5
1
phosphorylation
up-regulates activity
0.303
These results suggest that LARG is phosphorylated on tyrosine by FAK after stimulation with RGMa.
SIGNOR-279310
O95295
Q5S007
0
phosphorylation
down-regulates
0.514
Lrrk2 phosphorylates snapin and inhibits interaction of snapin with snap-25. these data suggest that lrrk2 may regulate neurotransmitter release via control of snapin function by inhibitory phosphorylation. hreonine 117 of snapin is one of the sites phosphorylated by lrrk2
SIGNOR-202436
O43318
P29350
0
dephosphorylation
down-regulates activity
0.295
Mechanistically, the association of EHEC Tir with SHP-1 facilitated the recruitment of SHP-1 to TAK1 and inhibited TAK1 phosphorylation, which then negatively regulated K63-linked polyubiquitination of TAK1 and downstream signal transduction.|SHP-1 inhibits TAK1 activity to down-regulate signal transduction and subsequent cytokine production.Innate immune responses are achieved by the activation of several pathogen-recognition receptors (PRPs), including TLRs, retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs).
SIGNOR-277128
P10451
P56178
0
transcriptional regulation
up-regulates quantity
0.373
Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis €œin vivo€.
SIGNOR-245340
P17655
P28482
0
phosphorylation
up-regulates
0.628
Epidermal growth factor activates m-calpain (calpain ii), at least in part, by extracellular signal-regulated kinase-mediated phosphorylation.We now show that erk directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (egf)-induced calpain activation in vitro and in vivo.
SIGNOR-123079
P23443
Q53EL6
1
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
O14578
Q9NQS7
1
phosphorylation
up-regulates activity
0.426
Figure 5.CIT-K phosphorylates INCENP. (a) Schematic diagram of INCENP structure illustrating the phosphorylated sites identified by MS.
SIGNOR-280232
Q9Y6M0
O60216
1
cleavage
up-regulates
0.2
Rad21 is a component of the cohesin complex that holds sister chromatids together during mitosis and repairs double-strand dna breaks. Interestingly, rad21 is cleaved by a caspase-like esp1/separase at the onset of anaphase to trigger sister chromatid separation.
SIGNOR-115426
O43561
O00506
0
phosphorylation
up-regulates activity
0.2
In sum, these data reveal that STK25 activates LATS kinases through a mechanism that is distinct from what has been characterized for the MAP4K/MST kinases (Fig.\u00a0 xref ).|Mechanistically, we demonstrate that STK25 promotes LATS phosphorylation at the activation loop in the absence of hydrophobic motif phosphorylation, which distinguishes it from all of the other known LATS-activating kinases discovered to date.
SIGNOR-279294
O96017
P61289
1
phosphorylation
up-regulates activity
0.349
REGγ interacts with DBC1 and is phosphorylated by Chk2.
SIGNOR-273611
P31749
P46527
1
phosphorylation
down-regulates
0.85
Because Thr198-phosphorylated p27Kip1 was localized only in the cytoplasm, Akt might promote 14-3-3 binding to p27Kip1 by phosphorylation at Thr198, allowing its cytoplasmic localization and degradation.
SIGNOR-88294
Q5TCY1
Q16555
1
phosphorylation
up-regulates activity
0.243
TTBK1 induces complex formation of pCRMP2 with pTau.|These data suggest that TTBK1-induced T514 CRMP2 phosphorylation is dependent on both S522 phosphorylation by Cdk5 and T555 phosphorylation by RhoK.
SIGNOR-279313
P31751
P55211
1
phosphorylation
down-regulates
0.528
Akt phosphorylated recombinant casp9 in vitro on serine-196 and inhibited its protease activity
SIGNOR-61561
Q12800
Q00526
0
phosphorylation
down-regulates
0.264
In vitro, lsf is phosphorylated by cyclin e/cyclin-dependent kinase 2 (cdk2), cyclin c/cdk2, and cyclin c/cdk3, predominantly on s309. Phosphorylation by cyclin c/cyclin-dependent kinase 2 following mitogenic stimulation of murine fibroblasts inhibits transcriptional activity of lsf during g1 progression
SIGNOR-184164
Q9H8S9
Q13043
0
phosphorylation
up-regulates
0.9
Mob1, when phosphorylated by MST1/2, binds to the autoinhibitory motif in Lats1/2, which in turn leads to the phosphorylation of the Lats activation loop (Lats1 S909 and Lats2 S872) and thereby an increase of their kinase activity
SIGNOR-201306
Q5TEC6
Q9NRC8
0
deacetylation
up-regulates activity
0.2
Besides confirming the previously reported histone H3K18 deacylation activity, our results revealed that SIRT7 has an astonishingly high activity to catalyze deacylation of H3K36 and is also catalytically active to deacylate H3K37.
SIGNOR-275883
P35968
P35790
0
phosphorylation
down-regulates quantity by destabilization
0.249
Here, we show for the first time a possible mechanism by which CKI dependent phosphorylation of VEGFR2 at specific sites in its C-terminal tail triggers SCF beta-TRCP -mediated VEGFR2 ubiquitination and destruction.
SIGNOR-279029
O15327
P60484
1
dephosphorylation
down-regulates activity
0.632
In support, the increase in PTEN caused by INPP4B knockdown was associated with increased phosphorylation of the Ser380, Thr382, Thr383 and Ser385 cluster of the protein (XREF_FIG), which is known to increase PTEN half-life, in colon cancer cells.|Exogenous INPP4B could pull down and dephosphorylate endogenous PTEN, suggesting that effect of INPP4B on PTEN in colon cancer cells is not due to cell-type-specific characteristics of INPP4B per se.|INPP4B downregulates PTEN in colon cancer cells.
SIGNOR-277018
P23769
P37231
1
null
down-regulates activity
0.369
GATA2 interacts directly with PPARG and C/EBP a , which may deplete PPARG involved in the promotion of adipogenesis
SIGNOR-132949
O75925
P49841
0
phosphorylation
down-regulates quantity by destabilization
0.332
We discovered a ubiquitin E3 ligase, HECTD2, which ubiquitinated and mediated the degradation of PIAS1, thus increasing inflammation in an experimental pneumonia model. We found that GSK3β phosphorylation of PIAS1 provided a phosphodegron for HECTD2 targeting. 
SIGNOR-276923
P34947
P04637
1
phosphorylation
down-regulates
0.37
Grk5, but not grk2 or grk6, phosphorylates p53 at thr-55, which promotes the degradation of p53, leading to inhibition of p53-dependent apoptotic response to genotoxic damage.
SIGNOR-163707
Q9NP80
Q9BUB5
0
phosphorylation
up-regulates activity
0.2
Constitutively active MNK1 activates and phosphorylates iPLA2γ. Thus, complement-mediated activation of iPLA(2)γ is mediated via ERK and p38 pathways, and phosphorylation of Ser-511 and/or Ser-515 plays a key role in the catalytic activity and signaling of iPLA(2)γ.
SIGNOR-273677
O43464
Q07812
0
relocalization
up-regulates
0.313
Bax and/or bak-mediated release of pro-apoptotic mediators including smac/diablo and omi
SIGNOR-88590
P35568
O14920
0
phosphorylation
down-regulates activity
0.654
IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways.
SIGNOR-251297
Q9UPG8
Q8WUI4
0
deacetylation
down-regulates
0.258
Plag1 and plagl2 are also regulated by acetylation. They are acetylated and activated by p300 and deacetylated and repressed by hdac7.
SIGNOR-140953
P10070
Q92630
0
phosphorylation
down-regulates quantity by destabilization
0.3
DYRK2 directly phosphorylated Gli2 sequences and resulted in the loss of coexpressed GLI proteins, indicating that DYRK2 acts by inducing the phosphorylation and degradation of GLI proteins via the ubiquitin and proteasome pathway.
SIGNOR-279034
Q9H3D4
P00519
0
phosphorylation
up-regulates quantity by stabilization
0.543
In cell lines, upon cisplatin treatment, c-Abl phosphorylates TAp63 on specific tyrosine residues. Such modifications affect p63 stability and induce a p63-dependent activation of proapoptotic promoters.
SIGNOR-260934
Q8IXL6
Q8NBP7
1
phosphorylation
up-regulates activity
0.537
Herein, we report that Fam20C and Fam20A significantly eliminate the Furin-cleavage of PCSK9 (XREF_FIG, lanes 5, 6), thereby enhancing the pPCSK9 activity|Herein, we show that Fam20C phosphorylates PCSK9 at Serines 47, 666, 668 and 688.
SIGNOR-278935
P06730
Q9HBH9
0
phosphorylation
up-regulates
0.56
Inhibition of mammalian target of rapamycin induces phosphatidylinositol 3-kinase-dependent and mnk-mediated eukaryotic translation initiation factor 4e phosphorylation.Therefore, eif4e is considered a survival protein involved in cell cycle progression, cell transformation, and apoptotic resistance. Phosphorylation of eif4e (usually at ser209) increases its binding affinity for the cap of mrna and may also favor its entry into initiation complexes.
SIGNOR-157537
P43250
P30411
1
phosphorylation
down-regulates activity
0.288
Ligand-induced phosphorylation is found at Ser339 and Ser346/Ser348 that could be executed by several G protein-coupled receptor kinases. 32P labeling of peptide 3 containing pS346/pS348 was enhanced 1.5–3-fold as compared with mock-transfected cells in the order GRK6 < GRK5 < GRK2 < GRK4α < GRK3. several endogenous GRKs may phosphorylate the B2R and that the various GRKs, even without apparent effect on total GPCR phosphorylation levels, may induce distinct phosphorylation patterns with possible functional consequences for receptor desensitization and sequestration.
SIGNOR-251207
P15036
P21815
1
transcriptional regulation
up-regulates quantity by expression
0.2
Ets2 is expressed at high levels during the differentiation and matrix mineralization phases of MC3T3-E1 culture. In addition, several extracellular matrix (ECM) associated gene products are targets of Ets2. Some of these matrix associated genes include: bone sialoprotein, osteonectin, osteocalcin and osteopontin
SIGNOR-259873
P51812
P84243
1
phosphorylation
down-regulates activity
0.2
Phosphorylation at ser-11 (h3s10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or uv irradiation and result in the activation of genes, such as c-fos and c-jun.
SIGNOR-138471
Q16566
P16220
1
phosphorylation
up-regulates activity
0.708
Pka, ca2+-calmodulin-dependent kinase iv (camkiv), msk, p70s6k and rsk phosphorylate creb. All these kinases target CREB on S133 to activate CREB.
SIGNOR-102722
P84243
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-273173
P30411
P32298
0
phosphorylation
down-regulates activity
0.288
Expression of GRK4α drastically increased the basal level of32P incorporation into B2R. GRK4α elevated the basal phosphorylation of Ser339 and Ser346/Ser348. phosphorylation of specific residues was correlated with the initiation of receptor internalization and the regulation of its desensitization.
SIGNOR-251193
P17302
P17706
0
dephosphorylation
up-regulates
0.324
Tc-ptp dephosphorylates cx43 residues y247 and y265, dephosphorylation maintained cx43 gap junctions at the plaque and partially reversed the channel closure caused by v-src-mediated phosphorylation of cx43.
SIGNOR-205101