IdA
string
IdB
string
labels
int64
mechanism
string
effect
string
score
float64
sentence
string
signor_id
string
P12931
P51813
1
phosphorylation
up-regulates
0.535
Coexpression of v-src and etk led to a transphosphorylation on tyrosine 566 of etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of etk.
SIGNOR-75330
P01178
Q6IMN6
0
post transcriptional regulation
up-regulates quantity by stabilization
0.2
Transcriptional and post-transcriptional regulation of oxytocin and vasopressin gene expression by CREB3L1 and CAPRIN2|Altogether, the data indicate that CAPRIN2 binds Oxt mRNA |Therefore, we propose that CAPRIN2 facilitates post-transcriptional modifications that increase Oxt transcript stability.
SIGNOR-268556
P63000
Q9NYF5
0
gtpase-activating protein
down-regulates activity
0.435
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-260503
Q9NRC8
P04637
1
deacetylation
down-regulates
0.498
We found that sirt7 interacts with p53 and efficiently deacetylates p53 in vitro, which corresponds to hyperacetylation of p53 in vivo.
SIGNOR-160539
Q96PU4
P24385
1
ubiquitination
down-regulates quantity by destabilization
0.294
We found that NIRF directly ubiquitinated cyclins D1 and E1, as evidenced by the appearance of the tail (Fig. 4B). In summary, the above findings suggest that NIRF tightly cooperates with the core cell cycle machinery and induces G1 arrest, which is accompanied by ubiquitination of cyclins D1 and E1.
SIGNOR-271885
P16591
P10275
1
phosphorylation
up-regulates
0.259
Fer is required for il-6 mediated ar activation by phosphorylating ar tyrosine 223 and binding via its sh2 domain.
SIGNOR-194749
P12931
P01116
1
phosphorylation
up-regulates activity
0.658
Src phosphorylation promotes the intrinsic exchange rate of KRAS Q61H.|Wild-type and Q61H-mutant KRAS are both phosphorylated by Src on Tyr32 and Tyr64 and dephosphorylated by SHP2, however, SHP2i does not reduce ERK phosphorylation in KRAS Q61H cells.
SIGNOR-278990
Q8WUI4
Q7KZI7
0
phosphorylation
down-regulates
0.344
We further show that emk and c-tak1 phosphorylate class iia hdacs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function
SIGNOR-149583
P51955
Q99501
1
phosphorylation
up-regulates activity
0.2
Nek2A mediates G2/M phosphorylation of GAS2L1. GAS2L1 and its Ser352 phosphorylation are required for proper spindle organization and chromosome segregation. 
SIGNOR-273683
O00712
P23352
1
transcriptional regulation
down-regulates quantity
0.2
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-268878
P35372
P35626
0
phosphorylation
down-regulates activity
0.2
These results demonstrate that the T180A mutation probably blocks GRK3- and arr3-mediated desensitization of MOR by preventing a critical agonist-dependent receptor phosphorylation and suggest a novel GRK3 site of regulation not yet described for other G-protein-coupled receptors
SIGNOR-247915
P54646
P50552
1
phosphorylation
down-regulates
0.2
Pharmacological ampk inhibitors and activators and ampk mutants revealed that the kinase specifically targets residue thr-278 but not ser-157 or ser-239. Quantitative fluorescence-activated cell sorter analysis and serum response factor transcriptional reporter assays, which quantify the cellular f-/g-actin equilibrium, indicated that ampk-mediated vasp phosphorylation impaired actin stress fiber formation and altered cell morphology.
SIGNOR-150462
P35222
O15111
0
phosphorylation
up-regulates quantity
0.485
Interestingly, while IKK2 negatively regulates beta-catenin stability similar to GSK3beta, IKK1 seems to increase beta-catenin protein level and downstream signal, such as cyclin D1 transcription.|These results suggested IKK1 may phosphorylate beta-catenin at different residues and protect it from ubiquitination mediated degradation.
SIGNOR-280230
P21854
P29350
0
dephosphorylation
down-regulates
0.623
Our work clearly identifies cd72 as both an shp-1 binding protein (figure 1,figure 2) and a direct substrate for shp-1 in vivo (figure 3). As tyrosine phosphorylation of cd72 strongly correlates with the ability of the bcr to deliver growth-inhibitory/apoptosis-inducing signals (figure 4), our results suggest that shp-1-catalyzed dephosphorylation of cd72 may antagonize these signals.
SIGNOR-60155
P45984
P55957
1
phosphorylation
up-regulates activity
0.406
(c) The phosphorylation of recombinant Bid by JNK2 (in vitro kinase assay) prevents its cleavage by caspase-8
SIGNOR-279220
Q92993
P06493
0
phosphorylation
up-regulates
0.478
Moreover, app stabilized tip60 through cdk-dependent phosphorylation
SIGNOR-139653
Q00987
Q99466
1
ubiquitination
down-regulates
0.37
We demonstrate that the intracellular domain of notch 4 is targeted for ubiquitylation and hence degradation by the ubiquitin ligase mdm2.
SIGNOR-172826
P63000
Q9P2F6
0
gtpase-activating protein
down-regulates activity
0.436
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-260473
Q13363
Q13153
0
phosphorylation
down-regulates activity
0.403
Pak1 phosphorylates ctbp selectively on ser158 within a putative regulatory loop, triggering ctbp cellular redistribution and blocking ctbp ak1 superphosphorylates ctbp and inhibits ctbp dehydrogenase activitycorepressor functions.
SIGNOR-103943
P68400
Q16666
1
phosphorylation
up-regulates activity
0.321
Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). | Specific phosphorylation of IFI 16 Ser132 in HeLa cell extracts and by purified CK2 in vitro
SIGNOR-250902
P46527
Q14012
0
phosphorylation
up-regulates activity
0.305
We also demonstrate that i) CaMKI phosphorylates p27 at Thr157and Thr198 in human cells and at Thr170and Thr197in mouse cells to modulate its subcellular localization;|Collectively, these results suggest that CaMKI is involved in mediating G1 progression by promoting cyclin D1/cdk4 complex formation through site-specific p27 phosphorylation in human lung epithelia.
SIGNOR-261194
O96017
P62714
0
dephosphorylation
up-regulates activity
0.309
Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells|In response to DNA damage, Chk2 is initially phosphorylated at Thr-68, which leads to its full activation.
SIGNOR-248582
P50542
O00623
0
ubiquitination
up-regulates activity
0.653
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-253020
O14543
P42224
0
transcriptional regulation
up-regulates quantity by expression
0.677
Expression of SOCS1 and SOCS3 is regulated primarily by activation of STAT1 and STAT3, respectively, although their expression can be mediated through other signaling cascades, including the mitogen activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) pathways.
SIGNOR-249565
Q9HC98
Q96AP0
1
phosphorylation
up-regulates activity
0.2
NEK6-mediated phosphorylation of human TPP1 regulates telomere length through telomerase recruitment|Shelterin component TPP1 plays critical roles in chromosome end protection and telomere length regulation. Specifically, TPP1 contains an OB-fold domain that provides an interface to recruit telomerase.|
SIGNOR-264424
P10636
Q16816
0
phosphorylation
down-regulates activity
0.313
Muscle phosphorylase kinase phosphorylates Ser237, Ser262, Ser285, Ser305, and Ser352 of human tau. in vitro phosphorylation of tau on Ser262 alone strongly reduced the ability of tau to bind microtubules whereas the phosphorylation of many Ser/Thr-Pro motif sites of tau showed moderate effects on the binding of tau to microtubules
SIGNOR-250285
Q9UQM7
Q15796
1
phosphorylation
down-regulates
0.549
Smad2 is a target substrate for cam kinase ii in vitro at serine-110, -240, and -260. furthermore, cam kinase ii blocked nuclear accumulation of a smad2 and induced smad2-smad4 hetero-oligomerization independently of tgfbeta receptor activation, while preventing tgfbeta-dependent smad2-smad3 interactions.
SIGNOR-82970
P10071
Q13635
1
transcriptional regulation
up-regulates quantity by expression
0.709
GLI activators bind to GACCACCCA motif to regulate transcription of GLI1, PTCH1, PTCH2, HHIP1, MYCN, CCND1, CCND2, BCL2, CFLAR, FOXF1, FOXL1, PRDM1 (BLIMP1), JAG2, GREM1, and Follistatin
SIGNOR-188884
O60711
P07948
0
phosphorylation
up-regulates activity
0.375
Of a total of 11 tyrosine sites in LPXN, we mutated Tyr(22), Tyr(72), Tyr(198), and Tyr(257) to phenylalanine and demonstrated that LPXN was phosphorylated by Lyn only at Tyr(72) and that this tyrosine site is proximal to the LD3 domain. We further show that LPXN suppressed the secretion of interleukin-2 by BCR-activated A20 B cells and that this inhibition was abrogated in the Y72F LPXN mutant, indicating that the phosphorylation of Tyr(72) is critical for the biological function of LPXN.
SIGNOR-262892
Q9GZZ0
P05556
1
transcriptional regulation
up-regulates quantity by expression
0.2
Consistently, ITGB1 promoter activity was decreased by HOXD1 knockdown in ECs. Furthermore, we identified the putative HOXD1-binding sites in the promoter region of ITGB1. Together, these findings suggest that HOXD1 plays a significant role in EC functions by regulating the expression of ITGB1.
SIGNOR-261648
P45983
Q9H2B2
1
phosphorylation
up-regulates activity
0.411
JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.
SIGNOR-273673
P52630
Q5T197
0
ubiquitination
down-regulates activity
0.448
DCST1 promotes ubiquitination of STAT2.|The ability of DCST1 to degrade STAT2 levels was visible both in the presence and absence of IFNbetastimulation.|In our study, DCST1 was found to interact with and promote ubiquitination of STAT2, leading to reduced STAT2 expression and attenuated activation of the ISG induction pathway.
SIGNOR-278747
Q86WV6
Q9BRZ2
0
ubiquitination
up-regulates activity
0.2
In contrast, we found that TRIM56 preferentially promoted K63 linked ubiquitination of the same lysine residue of STING that was important for the dimer formation and TBK1 activation.|Specifically, TRIM56 induces STING dimerization during dsDNA triggered signaling to potentiate antiviral responses while RNF5 may induce degradation of mitochondrial STING to suppress RLR induced antiviral responses.The findings that TRIM56 failed to interact with dsDNA and that there was no colocalization between TRIM56 and dsDNA within cells suggest that TRIM56 is unlikely to be a dsDNA sensor, and instead facilitates the STING function by ubiquitination.
SIGNOR-278621
P36894
Q15797
1
phosphorylation
up-regulates activity
0.732
Two types of bmp-induced signaling pathways are known, the smad and p38 mapk pathways. In the former case, bmpr1 phosphorylates smad-1,-5,-8, which forms a complex with smad4 that translocates into the nucleus and regulates gene expression.
SIGNOR-255263
P04637
Q9H2G2
0
phosphorylation
up-regulates activity
0.256
The Ste20 like kinase SLK promotes p53 transactivation and apoptosis.|Thus SLK induces p53 phosphorylation and transactivation, which enhances apoptosis after in vitro ischemia-reperfusion injury.
SIGNOR-279285
P12931
P16662
1
phosphorylation
up-regulates
0.343
Overexpression of regular or active src, but not dominant-negative src, in 2b7-transfected cos-1 cells increased 2b7 activity and phospho-y438-2b7 by 50%
SIGNOR-184613
Q96A00
Q13418
0
phosphorylation
up-regulates activity
0.549
Phosphopeptide mapping, phospho amino acid analysis and immunoblotting using phospho-specific antibodies indicated that ilk predominantly phosphorylated the site critical for potent inhibition, i.e. Thr(38) of cpi-17
SIGNOR-90828
Q16539
O43521
1
phosphorylation
down-regulates quantity by destabilization
0.32
Ser69 can also be phosphorylated by JNK and p38MAPK at least in vitro. Phosphorylation of BimEL on Ser69 promotes its ubiquitination.
SIGNOR-260442
Q00526
P06400
1
phosphorylation
down-regulates
0.443
The active form of prb is underphosphorylated. Cdk3/cyclin-c-mediated phosphorylation at ser-807 and ser-811 is required for g0-g1 transition.
SIGNOR-124212
Q9Y243
Q6ZVD8
0
dephosphorylation
down-regulates activity
0.683
The Abl kinase inhibitors and depletion of Bcr-Abl induced the expression of PHLPP1 and PHLPP2, which dephosphorylated Ser-473 on Akt1, -2, and -3, resulting in inhibited proliferation of CML cells.|Thus, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells.
SIGNOR-248731
Q86YJ5
Q12913
1
ubiquitination
down-regulates quantity by destabilization
0.2
MARCH9, a member of the RING-CH family of transmembrane E3 ubiquitin ligases, down-regulates CD4, major histocompatibility complex-I (MHC), and ICAM-1 in lymphoid cells. To identify novel MARCH9 substrates, we used high throughput flow cytometry and quantitative mass spectrometry by stable isotope labeling by amino acids in cell culture (SILAC) to determine the differential expression of plasma membrane proteins in a MARCH9-expressing B cell line. This combined approach identified 13 potential new MARCH9 targets. 
SIGNOR-271535
P08908
Q5BJH7
0
relocalization
up-regulates activity
0.399
Together, our results provide strong evidence that Yif1B is a member of the ER/Golgi trafficking machinery, which plays a key role in specific targeting of 5-HT(1A)R to the neuronal dendrites. This finding opens up new pathways for the study of 5-HT(1A)R regulation by partner proteins and for the development of novel antidepressant drugs.|We confirmed 5-HT(1A)R-Yif1B interaction by glutathione S-transferase pull-down experiments using rat brain extracts and transfected cell lines.
SIGNOR-268299
Q00987
Q13315
0
phosphorylation
down-regulates activity
0.756
Dephosphorylation stabilizes mdm2 and increases its affinity for p53, inducing p53 degredation. ;phosphorylated s260 and s395 ands260d and s395d mutant peptides inhibited binding of binding of a specific monoclonal antibody raised to mdm2. Phosphorylation of mdm2 regulates p53 degradation.
SIGNOR-94268
Q86TM6
P23786
1
ubiquitination
down-regulates quantity
0.2
Taken together, these data suggest that HRD1 selectively and specifically downregulates intracellular CPT2 levels.|These results demonstrate that HRD1 ubiquitinates CPT2, which is processed through Lys-48-linked ubiquitin chains.
SIGNOR-278723
Q13177
Q9BUB5
1
phosphorylation
down-regulates activity
0.42
Phosphorylation of Mnk1 by caspase-activated Pak2/gamma-PAK inhibits phosphorylation and interaction of eIF4G with Mnk. When 293T cells are subjected to apoptotic induction by hydrogen peroxide, Mnk1 is phosphorylated at both Thr(22) and Ser(27). These results indicate a role for Pak2 in the down-regulation of translation initiation in apoptosis by phosphorylation of Mnk1.
SIGNOR-250221
Q07954
P17252
0
phosphorylation
up-regulates
0.2
Serine and threonine phosphorylation of the low density lipoprotein receptor-related protein by protein kinase calpha regulates endocytosis and association with adaptor moleculesthese results indicate that elimination of serine and threonine phosphorylation sites in the lrp cytoplasmic domain reduces the extent of tyr63 phosphorylation and leads to impaired association with the adaptor protein shc.
SIGNOR-127215
P17676
P41440
1
transcriptional regulation
up-regulates quantity by expression
0.2
Collectively, these results identify transcriptionally important regions in the hRFC-C minimal promoter that include a GC-box and CCAAT-box, and suggest that cooperative interactions between Sp1 and C/EBP beta are essential for hRFC-C transactivation.
SIGNOR-254053
O75676
P01100
1
phosphorylation
up-regulates activity
0.392
Serine 374 and serine 362 are the primary sites targeted by Erk1/2 and the mitogen-activated protein kinase-activated kinases Rsk1/2 (12, 13, 37, 38, 41), respectively. Their phosphorylation leads to protein stabilization (3, 13, 20, 41). Threonine 325 and threonine 331 are secondary targets of Erk1/2; their modification occurs only when serines 362 and 374 are phosphorylated and Erk1/2 activation is sufficiently sustained (37, 38). This enhances the transcriptional activity of c-Fos
SIGNOR-263000
Q07869
P49840
0
phosphorylation
up-regulates activity
0.2
GSK-3alpha phosphorylates PPARalpha at Ser280, located in the ligand binding domain.|These results suggest that GSK-3alpha positively regulates PPARalpha activity through Ser280 phosphorylation.
SIGNOR-278515
Q07820
P27361
0
phosphorylation
up-regulates
0.436
We then showed that erk could phosphorylate mcl-1 at two consensus residues, thr 92 and 163, which is required for the association of mcl-1 and pin1, resulting in stabilization of mcl-1.
SIGNOR-179812
P27361
Q00613
1
phosphorylation
down-regulates
0.631
Sequential phosphorylation of hsf1 by mitogen-activated protein kinase and glycogen synthase kinase 3 at ser-303 and ser-307 represses transcriptional activation by heat shock factor-1.
SIGNOR-44999
P42345
P19484
1
phosphorylation
down-regulates activity
0.477
Our data points to the lysosome as the site where mTORC1-dependent phosphorylation of TFEB occurs. [...]Our study has revealed a specific role for phosphorylation of TFEB S211 in the negative regulation of the nuclear abundance of TFEB. This occurs through the promotion of 14-3-3 binding and the masking of the nearby NLS on TFEB.
SIGNOR-248270
P12931
Q16620
1
phosphorylation
up-regulates activity
0.46
Indeed, activated Src can directly phosphorylate recombinant TrkB protein in a cell-free system.|We found that both exogenous H 2 O 2 and endogenous ROS activate TrkB signaling by a Src family kinase dependent but brain derived neurotrophic factor independent mechanism in cultured rat cortical neurons.
SIGNOR-280130
P12931
P45984
0
phosphorylation
up-regulates activity
0.355
Activation of c-Src by JNK2 was accompanied by the phosphorylation of c-Src on threonine residue (s).|JNK2 directly phosphorylates c-Src and activates its auto phosphorylation.
SIGNOR-279221
P26358
P49841
0
phosphorylation
down-regulates quantity
0.272
We determined that in a human lung cell line, glycogen synthase kinase 3beta (GSK3beta) phosphorylated DNMT1 to recruit beta-transducin repeat-containing protein (betaTrCP), resulting in DNMT1 degradation, and that NNK activated AKT, inhibiting GSK3beta function and thereby attenuating DNMT1 degradation.
SIGNOR-279181
Q8N5S9
Q8IU85
1
phosphorylation
up-regulates activity
0.416
CaM-KIdelta exhibits Ca(2+)/CaM-dependent activity that is enhanced (approximately 30-fold) in vitro by phosphorylation of its Thr180 by CaM-K kinase (CaM-KK)alpha, consistent with detection of CaM-KIdelta-activating activity in HeLa cells. | This sustained activation of CaM-KIdelta was completely abolished by Thr180Ala mutation and inhibited by CaM-KK inhibitor, STO-609, indicating a functional CaM-KK/CaM-KIdelta cascade in HeLa cells.
SIGNOR-250715
Q9UBE8
Q12778
1
phosphorylation
down-regulates activity
0.613
Here, we report that the transforming growth factor-beta-activated kinase (TAK1)-Nemo-like kinase (NLK) pathway negatively regulates FOXO1. We show that NLK binds and phosphorylates FOXO1 at Pro-directed Ser/Thr residues in the transactivation domain. The phosphorylation by TAK1-NLK pathway inhibits the transcriptional activity of FOXO1 and excludes FOXO1 from the nucleus, which is independent of phosphatidylinositol 3-kinase/Akt pathway. 
SIGNOR-273907
Q13480
P28482
0
phosphorylation
up-regulates activity
0.602
Our results demonstrate that ERK1/2 phosphorylate Gab1 at six serine/threonine residues (T312, S381, S454, T476, S581, S597) in consensus motifs for MAP kinase phosphorylation. |serine and threonine phosphorylation are capable of modulating the initial signal
SIGNOR-249395
P12931
Q07666
1
phosphorylation
up-regulates activity
0.825
26 In particular, Sam68 was shown to play a scaffold role in Src kinase activated pathways, 16,27 and tyrosine phosphorylation of Sam68 by Src kinases triggers the release of bound RNA and might allow translational activation.
SIGNOR-279121
Q9Y4P1
Q01813
0
phosphorylation
up-regulates activity
0.2
In vitro kinase assay validated that PFKP functioning as a protein kinase phosphorylated ATG4B at S34. This phosphorylation could enhance ATG4B activity and p62 degradation. In addition, PFKP S386 phosphorylation was important to ATG4B S34 phosphorylation and autophagy in HEK293T cells.
SIGNOR-275832
Q9UKV0
Q9Y463
0
phosphorylation
down-regulates
0.2
Mirk activated mef2 not through direct phosphorylation of mef2 but by phosphorylation of its inhibitors, the class ii histone deacetylases (hdacs). Mef2 is sequestered by class ii hdacs such as hdac5 and mef2-interacting transcriptional repressor (mitr). Mirk antagonized the inhibition of mef2c by mitr, whereas kinase-inactive mirk was ineffective. Mirk phosphorylates class ii hdacs at a conserved site within the nuclear localization region, reducing their nuclear accumulation in a dose-dependent and kinase-dependent manner
SIGNOR-235813
Q9UPS8
Q01543
0
transcriptional regulation
down-regulates quantity by repression
0.284
In healthy individual, RUNX1/FLI1 complex negatively regulates ANKRD26 gene expression in MKs.
SIGNOR-266070
P42224
P22455
0
phosphorylation
up-regulates activity
0.348
Activation of Stat1 and Stat3 by FGFR derivatives. Lysates of 293T cells transfected as indicated were analysed by Western blotting using Phospho-Stat1 (Y701) antisera (top) or Stat1 antisera (bottom). (b) The same lysates in (a) were re-examined for phosphorylated Stat3 by Western blotting with Phospho-Stat3 (Y705) (top). all three FGFR family members examined here are able to lead to Stat activation. Expression of the 'TDII-like' derivatives of FGFR1, FGFR3, and FGFR4, as well as myrR1-WT, led to phosphorylation of both Stat1 and Stat3.
SIGNOR-251141
P41594
P05129
0
phosphorylation
up-regulates activity
0.415
Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca2+ oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839.
SIGNOR-249289
P12004
P00533
0
phosphorylation
up-regulates
0.341
Here, we show that the chromatin-bound pcna protein is phosphorylated on tyr 211, which is required for maintaining its function on chromatin and is dependent on the tyrosine kinase activity of egf receptor (egfr) in the nucleus. Phosphorylation on tyr 211 by egfr stabilizes chromatin-bound pcna protein and associated functions.
SIGNOR-150852
Q9HAU4
P12757
1
ubiquitination
down-regulates activity
0.738
Tgf-beta also induces the association of smurf2 with the transcriptional co-repressor snon and we show that smad2 can function to mediate this interaction. This allows smurf2 hect domain to target snon for ubiquitin-mediated degradation by the proteasome.
SIGNOR-236090
Q14247
P12931
0
phosphorylation
down-regulates activity
0.801
Erk phosphorylation and a mimicking S405,418D double mutation enhanced cortactin binding and activation of N-WASP. In contrast, Src phosphorylation inhibited the ability of cortactin previously phosphorylated by Erk, and that of S405,418D double mutant cortactin, to bind and activate N-WASP. Furthermore, Y-->D mutation of three tyrosine residues targeted by Src (Y421, Y466, and Y482) inhibited the ability of S405,418D cortactin to activate N-WASP.
SIGNOR-246513
Q6ZNE5
O75385
0
phosphorylation
up-regulates activity
0.651
ULK1 phosphorylates ATG14 at serine 29.
SIGNOR-278433
P62140
Q00987
1
dephosphorylation
up-regulates quantity by stabilization
0.2
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-248577
P16234
P22681
0
ubiquitination
down-regulates quantity by destabilization
0.478
Cbl overexpression in nih3t3 cells enhanced the ubiquitination and degradation of the platelet-derived growth factor receptor-alpha (pdgfralpha)
SIGNOR-68024
O95863
Q13131
0
phosphorylation
up-regulates quantity by stabilization
0.2
Serines 11 and 92 participate in the control of snail1 stability and positively regulate snail1 repressive function and its interaction with msin3a corepressor. Furthermore, serines 11 and 92 are required for snail1-mediated emt and cell viability, respectively. Pka and ck2 have been characterized as the main kinases responsible for in vitro snail1 phosphorylation at serine 11 and 92, respectively.
SIGNOR-161779
O75874
Q12772
0
transcriptional regulation
up-regulates quantity by expression
0.277
IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells|evidence that IDH1 may regulate lipogenesis in hepatic cells
SIGNOR-253133
Q00536
P46527
1
phosphorylation
down-regulates quantity by destabilization
0.333
In vitro kinase assays showed PCTAIRE1 phosphorylates p27 at Ser10. PCTAIRE1 silencing modulated Ser10 phosphorylation on p27 and led to its accumulation in cancer cells but not in nontransformed cells.|Together our findings reveal an unexpected role for PCTAIRE1 in regulating p27 stability, mitosis, and tumor growth, suggesting PCTAIRE1 as a candidate cancer therapeutic target.
SIGNOR-273016
Q2T9J0
Q86WA8
0
cleavage
down-regulates quantity by destabilization
0.66
Self-cleavage of Tysnd1 in the active oligomer most likely inactivates its protease activity. Subsequently, the cleaved products are degraded by PsLon and removed from the Tysnd1 oligomer.
SIGNOR-261054
Q14185
P63000
1
guanine nucleotide exchange factor
up-regulates activity
0.735
We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth.
SIGNOR-266822
Q13315
Q14694
1
phosphorylation
up-regulates quantity by stabilization
0.252
The translocation and stabilization of USP10 is regulated by ATM -mediated phosphorylation of USP10 at Thr42 and Ser337. 
SIGNOR-276276
O43865
O15530
0
phosphorylation
down-regulates activity
0.2
Residue 68 resides in a consensus phosphorylation site for PKD (Figure 1A) [22,23]. Interestingly, phosphorylation of Ser68 could allow for subsequent phosphorylation of Ser71, Ser74, Ser77 and Ser80 by CK1, for which the consensus phosphorylation site is pS/T-X-X-S/T| We found that phosphorylation of Ser71 and Ser74 were sufficient to enable inhibition of IP3 binding to the IP3R
SIGNOR-249174
E9PAV3
P49841
0
phosphorylation
down-regulates
0.2
Gsk3 beta-dependent phosphorylation of the alpha nac coactivator regulates its nuclear translocation and proteasome-mediated degradation.
SIGNOR-123262
P78527
P16104
1
phosphorylation
up-regulates
0.2
Dna-dependentprotein_ kinase_ (dna-pk) that phosphorylate h2ax at dsbs
SIGNOR-192443
Q13315
Q9NPI1
1
phosphorylation
down-regulates activity
0.2
ATM Directly Phosphorylates BRD7 at Ser 263 Site.
SIGNOR-279780
Q96MT8
P24941
1
relocalization
up-regulates activity
0.372
Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome.
SIGNOR-271725
P29376
P35568
1
phosphorylation
up-regulates
0.314
Recently, we demonstrated that ltk utilizes shc and irs-1 as two major substrates and while both equally activate the ras pathway, only irs-1 suppresses apoptosis of hematopoietic cells.
SIGNOR-49531
Q16695
Q9UPS6
0
methylation
down-regulates activity
0.2
SETD1B encodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks.
SIGNOR-265577
P06239
Q8IWV1
1
phosphorylation
up-regulates activity
0.399
Upon stimulation via the B or T cell receptors, LAX is rapidly phosphorylated by Src and Syk family tyrosine kinases and interacts with Grb2, Gads, and p85. 
SIGNOR-273528
Q92481
Q15139
0
phosphorylation
down-regulates activity
0.295
Mechanistically, we observed that PKD phosphorylates AP2\u03b2 at Ser-258 and Ser-277 and suppresses its nuclear accumulation.|Using ChIP analyses, here we found that PKD knockdown in HUVECs increases binding of AP2beta to the VEGFR-2 promoter.
SIGNOR-279267
P78527
O96017
1
phosphorylation
up-regulates
0.59
We have found that dna-pk is the major constituent of an activity present in extracts of mammalian cells that phosphorylates chk2. Our results suggest that hypophosphorylated chk2 can be phosphorylated at thr68 by dna-pk in vitro.
SIGNOR-133384
Q96Q15
P04637
1
phosphorylation
up-regulates
0.411
Hsmg-1 is a stress-activated kinase that phosphorylates p53 and hupf1 in vitrothe observation that hsmg-1 exhibits p53 (ser-15) kinase activity in vitro suggested that this pikk might be involved in genotoxic stress-induced p53 phosphorylation and stabilization in intact cells.
SIGNOR-125135
P45983
O75581
1
phosphorylation
up-regulates
0.382
We show that several proline-directed mitogen-activated protein kinases (mapks), such as p38, erk1/2, and jnk1 are sufficient and required for the phosphorylation of ppps/tp motifs of lrp6. External stimuli, which control the activity of mapks, such as phorbol esters and fibroblast growth factor 2 (fgf2) control the choice of the lrp6-ppps/tp kinase and regulate the amplitude of lrp6 phosphorylation and wnt/beta-catenin-dependent transcription.
SIGNOR-169007
Q9NWB1
P51608
0
transcriptional regulation
down-regulates quantity by repression
0.28
MeCP2 binds to the promoter region of six target genes. ChIP with anti-MeCP2 antibody shows that MeCP2 binds to the promoter regions of activated targets Sst, Oprk1, Gamt, and Gprin1, and repressed targets Mef2c and A2bp1.
SIGNOR-264681
O60664
P11717
1
relocalization
up-regulates activity
0.725
TIP47 is present in cytosol and on endosomes and is required for MPR transport from endosomes to the trans-Golgi network in vitro and in vivo. TIP47 recognizes a phenylalanine/tryptophan signal in the tail of the cation-dependent MPR that is essential for its proper sorting within the endosomal pathway. These data suggest that TIP47 binds MPR cytoplasmic domains and facilitates their collection into transport vesicles destined for the Golgi.
SIGNOR-253092
P15172
P35354
0
null
up-regulates
0.264
Furthermore, COX-2 inhibition reduced MyoD expression in regenerating muscle, suggesting a role for COX-2 in modulating muscle differentiation, as well as growth
SIGNOR-256214
P48730
Q9UJU2
1
phosphorylation
down-regulates
0.25
Cki_/_ binds and phosphorylates lef-1, and this phosphorylation disrupts lef-1_-catenin interaction
SIGNOR-134494
P04637
O15264
0
phosphorylation
up-regulates
0.462
In mcf-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at ser33 and ser46, a newly identified site.
SIGNOR-72691
Q9H3D4
Q16539
0
phosphorylation
down-regulates quantity by destabilization
0.307
P38α phosphorylates and destabilizes p63.
SIGNOR-277414 
Q53EL6
Q9Y297
0
ubiquitination
down-regulates
0.425
Both akt and p70(s6k) phosphorylate pdcd4, allowing for binding of the e3-ubiquitin ligase beta-trcp and consequently ubiquitylation.
SIGNOR-160985
Q8IW41
P28482
0
phosphorylation
up-regulates
0.48
Activated following phosphorylation at thr-182 by p38-alpha/mapk14, p38-beta/mapk11, erk2/mapk1, erk3/mapk6, and erk4/mapk4.
SIGNOR-58127
Q13546
Q8WZ73
0
ubiquitination
down-regulates quantity by destabilization
0.468
We report that CARP-2, a RING domain-containing ubiquitin protein ligase (E3), is a negative regulator of TNF-induced NF-kappaB activation. By virtue of its phospholipid-binding FYVE domain, CARP-2 localized to endocytic vesicles, where it interacted with internalized TNF-receptor complex, resulting in RIP ubiquitination and degradation.
SIGNOR-271482
Q05655
O95817
1
phosphorylation
up-regulates
0.251
Pkc_-mediated phosphorylation of bag3 at ser187 site induces epithelial-mesenchymal transition and enhances invasiveness in thyroid cancer fro cells. we showed that bag3 was implicated in epithelial-mesenchymal transition (emt) procedure, and phosphorylation state at ser187 site had a critical role in emt regulation by bag3.
SIGNOR-199316
O00418
Q15418
0
phosphorylation
down-regulates activity
0.513
We show that two such kinases, p70 s6 kinase (regulated via mtor) and p90(rsk1) (activated by erk), phosphorylate eef2k at a conserved serine and inhibit its activity
SIGNOR-109708
Q2TAL8
Q5ST30
1
transcriptional regulation
up-regulates quantity by expression
0.2
QRICH1 promotes the expression of translation-related genes. our combined ChIP-seq and RNA-seq analyses identified that QRICH1 and ATF4 were enriched at the promoters of these specific tRNA synthetases, and that ER stress positively regulated their transcription (Fig. 4I). Together, these findings suggest that QRICH1 and ATF4 modulate tRNA metabolic processes to promote secreted protein synthesis during ER stress.
SIGNOR-269409