GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	labels float64 0 2	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
O00203	Q9Y496	1	binding	up-regulates activity	0.371	Here, we show that the beta subunit of AP-3, a clathrin-associated protein complex required for HIV-1 release, is a target of IP(7)-mediated pyrophosphorylation. We have identified Kif3A, a motor protein of the kinesin superfamily, as an AP3B1-binding partner and demonstrate that Kif3A, like the AP-3 complex, is involved in an intracellular process required for HIV-1 Gag release.	SIGNOR-260398
Q8N6T7	P36956	1	binding	up-regulates activity	0.371	SIRT6 directs chromatin recruitment of CLOCK:BMAL1 and SREBP1.Importantly, SIRT6 also controls SREBP-1 recruitment to target promoters, such as Fasn, and helps maintain proper cyclic transcription. In fact, circadian metabolomics analyses reveal that SIRT6 controls lipid metabolism, contributing to the regulation of pathways involved in fatty acid synthesis and beta oxidation, triglyceride storage, signaling, and cellular membrane lipids.	SIGNOR-268158
P53350	Q14790	1	phosphorylation	down-regulates quantity by destabilization	0.371	By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis.	SIGNOR-272989
Q5S007	P53805	1	phosphorylation	up-regulates activity	0.371	LRRK2 Directly Phosphorylates RCAN1.	SIGNOR-278340
Q13351	Q01543	2	binding	down-regulates activity	0.371	The present study also shows that EKLF itself inhibits FLI-1 activity. As suggested above for the inhibition of EKLF activity, the inhibition of FLI-1 activity most probably involves the indirect recruitment of EKLF to FLI-1 target promoters by protein-protein interaction.	SIGNOR-256046
Q9BXM7	Q6NUN9	1	phosphorylation	up-regulates activity	0.37	PINK1 directly phosphorylates PARIS at S322 and S613, priming it for ubiquitination by Parkin, which interacts with the C-terminus zinc finger of PARIS and tags it for destruction [ xref \u2013 xref , xref ].\|Thus, by tagging PARIS for destruction, PINK1/Parkin drive the generation of new mitochondria by increasing PGC-1\u03b1 levels (Fig. 1d).	SIGNOR-278268
Q9NVW2	P01106	1	ubiquitination	down-regulates quantity by destabilization	0.37	This suggests that RLIM negatively regulates the transcriptional activity of c-Myc.\|We further showed that RLIM can promote polyubiquitination of c-Myc in cells.	SIGNOR-278551
Q9P1W9	P14618	1	phosphorylation	up-regulates quantity by stabilization	0.37	Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis	SIGNOR-267472
P51955	Q96CN5	1	phosphorylation	down-regulates activity	0.37	Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.	SIGNOR-273707
Q07912	Q9Y4C1	1	phosphorylation	down-regulates activity	0.37	We report that ACK1 phosphorylates the ER co-activator, KDM3A, a H3K9 demethylase, at an evolutionary conserved tyrosine 1114 site in a heregulin-dependent manner, even in the presence of tamoxifen.	SIGNOR-276842
P33981	Q9Y5T5	1	phosphorylation	down-regulates quantity by destabilization	0.37	Usp16 is a TTK phosphorylation substrate.	SIGNOR-277351
P17252	P23677	1	null	down-regulates activity	0.37	In contrast, phosphorylation of the A isoform with PKC caused a significant decrease in activity whether assayed in the presence or absence of calcium/calmodulin (to _25% of the unphosphorylated enzyme activity).	SIGNOR-248991
O14920	Q13568	1	phosphorylation	up-regulates activity	0.37	Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.\|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.	SIGNOR-279466
Q9HAU4	Q13887	1	ubiquitination	down-regulates quantity by destabilization	0.37	Consistent with these observations, another study documented that Smurf2 specifically destabilizes KLF5, that the degradation of KLF5 by Smurf2 is disrupted by the proteasome inhibitor MG132, and that Smurf2 ubiquitinates KLF5 .	SIGNOR-278781
Q9P2P5	O15350	1	ubiquitination	up-regulates quantity by stabilization	0.37	P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.	SIGNOR-269457
O14920	P31946	1	phosphorylation	down-regulates	0.37	We provide a mechanism for these observations through the phosphorylation of 14-3-3beta by ikkbeta and pkcdelta on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.	SIGNOR-138608
Q96AC1	P12931	2	binding	up-regulates activity	0.37	Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration.	SIGNOR-266101
P01106	P52789	1	transcriptional regulation	up-regulates quantity	0.37	Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.	SIGNOR-259986
Q9NT99	P78352	1	binding	up-regulates activity	0.37	A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles	SIGNOR-264052
P16220	P01189	1	transcriptional regulation	up-regulates quantity by expression	0.37	Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein\|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.	SIGNOR-268620
Q99750	P13349	1	binding	down-regulates activity	0.37	We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals.	SIGNOR-240433
P68400	Q00613	1	phosphorylation	up-regulates activity	0.37	Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.	SIGNOR-250898
P19784	Q13144	1	phosphorylation	up-regulates activity	0.37	Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.	SIGNOR-250990
P10398	Q15796	1	phosphorylation	down-regulates quantity by destabilization	0.37	Araf promotes Smad2 linker phosphorylation through S253.\|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2.	SIGNOR-279391
P04150	P41235	1	transcriptional regulation	up-regulates quantity by expression	0.37	Electrophoretic mobility shift, chromatin immunoprecipitation (ChIP), and streptavidin DNA binding assays revealed that DEX increased binding of HNF4alpha to the HNF4-RE and that an interaction of GR and HNF4alpha occurred at this site.	SIGNOR-251684
P35637	Q16637	1	relocalization	up-regulates activity	0.37	Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.\|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 \|Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells	SIGNOR-262107
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
P80370	P02751	1	binding	up-regulates	0.37	We show a direct interaction of pref-1 and fibronectin via the pref-1 juxtamembrane domain and fibronectin c-terminal domain	SIGNOR-165347
O00165	P16615	1	binding	down-regulates quantity by destabilization	0.37	The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival.\|Importantly, HAX-1 overexpression was associated with down-regulation of SERCA2 expression levels, resulting in significant reduction of apparent ER Ca(2+) levels.	SIGNOR-262052
P06493	P49459	1	phosphorylation	up-regulates	0.37	Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.	SIGNOR-116504
Q00987	Q9NXV6	1	ubiquitination	down-regulates	0.37	Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.	SIGNOR-160974
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
Q9HCI7	P04637	1	ubiquitination	down-regulates activity	0.37	Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.	SIGNOR-271774
Q9NZS9	Q14790	1	binding	down-regulates	0.37	We also demonstrate that the mitochondrial protein bar, which has been shown to simultaneously bind caspase-8 and bcl-2	SIGNOR-112585
P12931	Q96AC1	2	phosphorylation	up-regulates activity	0.37	Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration.	SIGNOR-266100
Q05513	P41594	1	phosphorylation	up-regulates activity	0.37	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-249284
P18146	Q9Y251	1	transcriptional regulation	up-regulates quantity by expression	0.37	Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.	SIGNOR-254267
Q9UHD2	Q99558	1	phosphorylation	down-regulates quantity by destabilization	0.37	TBK1 induces NIK phosphorylation and degradation.	SIGNOR-279767
Q13490	Q9Y385	1	ubiquitination	down-regulates quantity by destabilization	0.37	We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome.	SIGNOR-263092
P48729	Q9UKV8	1	phosphorylation	down-regulates activity	0.369	Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.	SIGNOR-276510
P07333	P16885	1	null	up-regulates	0.369	Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway	SIGNOR-255570
P24941	Q01167	1	phosphorylation	up-regulates	0.369	We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.	SIGNOR-167834
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
Q9H2P0	Q9GZQ8	1	binding	up-regulates activity	0.369	Here, we show for the first time that hippocampal ADNP deficiency paralleled reduced beclin1 expression which, in turn, parallels increased tauopathy and cell death. We now show that ADNP directly interacts with LC3B, implicating the requirement of a healthy ADNP system for the apoptotic/autophagy processes.	SIGNOR-266759
P29376	P22681	1	phosphorylation	up-regulates	0.369	Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.	SIGNOR-49528
O00327	Q9UJ55	1	binding	down-regulates activity	0.369	Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.	SIGNOR-253517
Q76NI1	P11137	1	phosphorylation	up-regulates activity	0.369	V-KIND enhances Thr phosphorylation of MAP2.	SIGNOR-278950
P31749	P15559	1	phosphorylation	down-regulates quantity by destabilization	0.369	Akt phosphorylates NQO1 on S40 and T128 residues. Here we show that Akt phosphorylates NQO1 at T128 residues and triggers its polyubiquitination and proteasomal degradation, abrogating its antioxidative effects in PD. Akt binds NQO1 in a phosphorylation-dependent manner. Interestingly, Akt, but not PINK1, provokes NQO1 phosphorylation and polyubiquitination with Parkin as an E3 ligase.	SIGNOR-276868
Q9UQM7	P11831	1	phosphorylation	up-regulates activity	0.369	Skeletal muscle CaMKII enriches in nuclei and phosphorylates myogenic factor SRF at multiple sites. \| Microsequencing of these phosphorylated peptides identified that both Ser-103 and a novel residue, Thr-160 in the MADS box of SRF, were sites of phosphorylation. \| The location of Thr-160 in the 3-D structure of SRF suggests that its phosphorylation by nuclear CaMKII may directly influence DNA binding of SRF and other MADS box factors.	SIGNOR-250639
P28482	P42702	1	phosphorylation	down-regulates	0.369	Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro	SIGNOR-32753
Q00526	Q14934	1	phosphorylation	up-regulates activity	0.369	CDK3 enhances the transactivation and transcription activity of NFAT3.\|NFAT3 can be phosphorylated by CDK3 at Ser259, which is critical for its transactivation activity and cell transformation.	SIGNOR-278511
Q9H4B4	P05412	1	phosphorylation	up-regulates	0.369	Stress-induced c-jun activation mediated by polo-like kinase 3 in corneal epithelial cells. Hypoxia/reoxygenation activated plk3 in hce cells to directly phosphorylate c-jun proteins at phosphorylation sites ser-63 and ser-73, and to increase dna binding activity of c-jun.	SIGNOR-157721
O14733	P35568	1	phosphorylation	down-regulates activity	0.369	Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase	SIGNOR-217920
P45983	Q96P20	1	phosphorylation	up-regulates activity	0.369	Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.\|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ].	SIGNOR-280034
Q15418	Q15653	1	phosphorylation	down-regulates quantity by destabilization	0.369	By using recombinant wild-type and mutant IkappaBbeta proteins, both active ERK2 and RSK1 were found to directly phosphorylate IkappaBbeta, but only active RSK1 phosphorylated IkappaBbeta on Ser19 and Ser23, two sites known to mediate the subsequent ubiquitination and degradation.	SIGNOR-280114
P28482	P68400	1	phosphorylation	up-regulates	0.369	Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity	SIGNOR-161855
P51812	Q14790	1	phosphorylation	down-regulates quantity by destabilization	0.369	The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability.	SIGNOR-272997
Q9H4M3	P38398	1	binding	down-regulates quantity by destabilization	0.369	The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.	SIGNOR-272037
Q12913	P19174	1	dephosphorylation	down-regulates	0.369	Cd148 can dephosphorylate lat and plc?1 In vitro. / plc?1 Undergoes inducible tyrosine phosphorylation following tcr stimulation (46), and this phosphorylation is required to stimulate its catalytic activity	SIGNOR-105790
Q86Y07	Q13469	1	phosphorylation	up-regulates	0.369	We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.	SIGNOR-199263
Q99801	Q13547	1	binding	down-regulates activity	0.369	NKX3.1 also binds HDAC1 and releases p53 from p53-MDM2-HDAC1 complex, promoting p53 acetylation and activity.	SIGNOR-251549
P53355	Q13526	1	phosphorylation	down-regulates activity	0.369	DAPK1 inhibits Pin1 nuclear localization and cellular function.\|DAPK1 interacts with and phosphorylates Pin1 on Ser71 in vitro and in vivo.	SIGNOR-278160
Q9UDY2	O00192	1	relocalization	down-regulates activity	0.369	We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression	SIGNOR-252122
P28482	Q9Y463	1	phosphorylation	up-regulates activity	0.369	S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro.	SIGNOR-276937
Q13884	P53778	1	binding	down-regulates	0.368	Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation	SIGNOR-255901
Q05513	P31946	1	phosphorylation	down-regulates activity	0.368	Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f.	SIGNOR-249035
P28482	P12036	1	phosphorylation	up-regulates activity	0.368	The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. \|Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.	SIGNOR-249424
P06493	O00418	1	phosphorylation	down-regulates	0.368	Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis	SIGNOR-177982
P46934	Q96GG9	1	monoubiquitination	up-regulates quantity	0.368	Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1,	SIGNOR-272719
Q13535	Q92900	1	phosphorylation	up-regulates activity	0.368	Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.	SIGNOR-278911
P49840	Q13144	1	phosphorylation	down-regulates activity	0.368	We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B	SIGNOR-251215
Q13547	O43524	1	deacetylation	up-regulates activity	0.368	The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a	SIGNOR-256486
Q7L7X3	Q13043	1	phosphorylation	up-regulates	0.368	In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.	SIGNOR-201324
Q16539	Q6STE5	1	phosphorylation	up-regulates activity	0.368	P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci.	SIGNOR-176557
P45983	Q9H211	1	phosphorylation	up-regulates quantity by stabilization	0.368	We discovered that human Cdt1, an essential origin licensing protein whose activity must be restricted to G(1) phase, is a substrate of the stress-activated mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). These MAP kinases phosphorylate Cdt1 both during unperturbed G(2) phase and during an acute stress response. Phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation during S phase and after DNA damage by blocking Cdt1 binding to the Cul4 adaptor, Cdt2.	SIGNOR-276361
P29350	P08922	1	dephosphorylation	down-regulates	0.368	Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.	SIGNOR-105922
O00408	P17612	1	binding	down-regulates activity	0.368	We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.	SIGNOR-275730
O94889	O14965	1	binding	up-regulates activity	0.368	We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes.We also noticed that overexpression of both CUL3 and KLHL18 stimulated mono-ubiquitylation of Aurora-A as well (Fig. 8A,B).	SIGNOR-272021
P68400	P45973	1	phosphorylation	up-regulates	0.368	Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.	SIGNOR-171707
P06493	Q9Y6Q9	1	phosphorylation	down-regulates	0.368	We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.	SIGNOR-195233
Q9ULU8	P60880	1	binding	up-regulates activity	0.368	CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1	SIGNOR-264338
P10747	P48736	1	binding	up-regulates	0.368	Cd28 can bind directly to pi3k by a well-characterized ymnm binding motif in its cytoplasmic domain.	SIGNOR-159322
P17612	P07101	1	phosphorylation	up-regulates activity	0.368	HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins.	SIGNOR-250061
Q99873	P62633	1	methylation	down-regulates	0.368	Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding	SIGNOR-204958
P27361	O15525	1	phosphorylation	up-regulates quantity	0.368	By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.\|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.	SIGNOR-280027
Q8WTV0	P12931	1	binding	up-regulates activity	0.368	Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages.	SIGNOR-260314
P07332	P11274	1	phosphorylation	down-regulates activity	0.368	In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.	SIGNOR-251137
P39880	Q96FE7	1	transcriptional regulation	down-regulates quantity by repression	0.368	We demonstrate that CUX1 deficiency activates phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), leading to increased tumor growth and susceptibility to PI3K-AKT inhibition.	SIGNOR-260072
Q14790	P49768	1	cleavage	up-regulates activity	0.368	Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.	SIGNOR-261760
Q92949	Q9UI46	1	transcriptional regulation	up-regulates quantity by expression	0.368	FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).	SIGNOR-266932
Q96GD4	P25490	1	phosphorylation	up-regulates	0.368	Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1	SIGNOR-200079
Q05655	P00533	1	phosphorylation	down-regulates activity	0.368	These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling.	SIGNOR-248858
P49841	Q13887	1	phosphorylation	down-regulates	0.368	Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5	SIGNOR-203627
O43474	P11831	1	binding	down-regulates	0.368	Klf4 antagonizes contractile gene expression through diverse mechanisms including (i) inhibiting the binding of srf-myocd or srf-mrtfs to the carg box by direct association with srf.	SIGNOR-174258
P51812	P25963	1	phosphorylation	down-regulates quantity by destabilization	0.368	Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.	SIGNOR-279108
P12931	P15498	1	phosphorylation	up-regulates activity	0.368	These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.\|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).	SIGNOR-279124
P28482	Q05469	1	phosphorylation	up-regulates activity	0.368	Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.	SIGNOR-249413
Q00535	O14939	1	phosphorylation	up-regulates activity	0.368	In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.\|We determined that Cdk5 phosphorylates PLD2 at Ser 134 of PLD2 and that this phosphorylation was suggested to be important for EGF-dependent insulin secretion.	SIGNOR-278395
P06493	P12830	1	phosphorylation	up-regulates activity	0.368	We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.\|We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.	SIGNOR-280204
P31749	P23396	1	phosphorylation	up-regulates activity	0.368	Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.	SIGNOR-259815

O00203

Q9Y496

1

binding

up-regulates activity

0.371

Here, we show that the beta subunit of AP-3, a clathrin-associated protein complex required for HIV-1 release, is a target of IP(7)-mediated pyrophosphorylation. We have identified Kif3A, a motor protein of the kinesin superfamily, as an AP3B1-binding partner and demonstrate that Kif3A, like the AP-3 complex, is involved in an intracellular process required for HIV-1 Gag release.

SIGNOR-260398

Q8N6T7

P36956

1

binding

up-regulates activity

0.371

SIRT6 directs chromatin recruitment of CLOCK:BMAL1 and SREBP1.Importantly, SIRT6 also controls SREBP-1 recruitment to target promoters, such as Fasn, and helps maintain proper cyclic transcription. In fact, circadian metabolomics analyses reveal that SIRT6 controls lipid metabolism, contributing to the regulation of pathways involved in fatty acid synthesis and beta oxidation, triglyceride storage, signaling, and cellular membrane lipids.

SIGNOR-268158

P53350

Q14790

1

phosphorylation

down-regulates quantity by destabilization

0.371

By phosphorylating S387 in procaspase-8 Cdk1/cyclin B1 generates a phospho-epitope for the binding of the PBD of Plk1. Subsequently, S305 in procaspase-8 is phosphorylated by Plk1 during mitosis. Using an RNAi-based strategy we could demonstrate that the extrinsic cell death is increased upon Fas-stimulation when endogenous caspase-8 is replaced by a mutant (S305A) mimicking the non-phosphorylated form. Together, our data show that sequential phosphorylation by Cdk1/cyclin B1 and Plk1 decreases the sensitivity of cells toward stimuli of the extrinsic pathway during mitosis.

SIGNOR-272989

Q5S007

P53805

1

phosphorylation

up-regulates activity

0.371

LRRK2 Directly Phosphorylates RCAN1.

SIGNOR-278340

Q13351

Q01543

2

binding

down-regulates activity

0.371

The present study also shows that EKLF itself inhibits FLI-1 activity. As suggested above for the inhibition of EKLF activity, the inhibition of FLI-1 activity most probably involves the indirect recruitment of EKLF to FLI-1 target promoters by protein-protein interaction.

SIGNOR-256046

Q9BXM7

Q6NUN9

1

phosphorylation

up-regulates activity

0.37

PINK1 directly phosphorylates PARIS at S322 and S613, priming it for ubiquitination by Parkin, which interacts with the C-terminus zinc finger of PARIS and tags it for destruction [ xref \u2013 xref , xref ].|Thus, by tagging PARIS for destruction, PINK1/Parkin drive the generation of new mitochondria by increasing PGC-1\u03b1 levels (Fig. 1d).

SIGNOR-278268

Q9NVW2

P01106

1

ubiquitination

down-regulates quantity by destabilization

0.37

This suggests that RLIM negatively regulates the transcriptional activity of c-Myc.|We further showed that RLIM can promote polyubiquitination of c-Myc in cells.

SIGNOR-278551

Q9P1W9

P14618

1

phosphorylation

up-regulates quantity by stabilization

0.37

Here, we identified the protein-serine/threonine kinase PIM2, a known oncogene, as a novel binding partner of PKM2. The interaction between PIM2 and PKM2 was confirmed by multiple biochemical approaches in vitro and in cultured cells. Importantly, we found that PIM2 could directly phosphorylate PKM2 on the Thr-454 residue, resulting in an increase of PKM2 protein levels. Compared with wild type, PKM2 with the phosphorylation-defective mutation displayed a reduced effect on glycolysis

SIGNOR-267472

P51955

Q96CN5

1

phosphorylation

down-regulates activity

0.37

Moreover, LRRC45 interacts with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber-like structures are significantly reduced, which subsequently leads to centrosome separation.

SIGNOR-273707

Q07912

Q9Y4C1

1

phosphorylation

down-regulates activity

0.37

We report that ACK1 phosphorylates the ER co-activator, KDM3A, a H3K9 demethylase, at an evolutionary conserved tyrosine 1114 site in a heregulin-dependent manner, even in the presence of tamoxifen.

SIGNOR-276842

P33981

Q9Y5T5

1

phosphorylation

down-regulates quantity by destabilization

0.37

Usp16 is a TTK phosphorylation substrate.

SIGNOR-277351

P17252

P23677

1

null

down-regulates activity

0.37

In contrast, phosphorylation of the A isoform with PKC caused a significant decrease in activity whether assayed in the presence or absence of calcium/calmodulin (to _25% of the unphosphorylated enzyme activity).

SIGNOR-248991

O14920

Q13568

1

phosphorylation

up-regulates activity

0.37

Here we present evidence that the kinase IKKbeta phosphorylates and activates IRF5 in response to stimulation in several inflammatory pathways, including those emanated from Toll like receptors and retinoic acid inducible gene I like receptors.|Recombinant IKK\u03b2 phosphorylated IRF5 at Ser-445 in vitro, and a point mutation of this serine abolished IRF5 activation and cytokine production.

SIGNOR-279466

Q9HAU4

Q13887

1

ubiquitination

down-regulates quantity by destabilization

0.37

Consistent with these observations, another study documented that Smurf2 specifically destabilizes KLF5, that the degradation of KLF5 by Smurf2 is disrupted by the proteasome inhibitor MG132, and that Smurf2 ubiquitinates KLF5 .

SIGNOR-278781

Q9P2P5

O15350

1

ubiquitination

up-regulates quantity by stabilization

0.37

P73 was efficiently ubiquitinated but stabilized in a NEDL2-dependent manner. Accordingly, p73 decayed at faster rates in the absence of NEDL2 than in its presence. Consistent with the NEDL2-mediated stabilization of p73, NEDL2 enhanced the p73-dependent transcriptional activation. Thus, our results suggest that NEDL2 activates the function of p73 by increasing its stability.

SIGNOR-269457

O14920

P31946

1

phosphorylation

down-regulates

0.37

We provide a mechanism for these observations through the phosphorylation of 14-3-3beta by ikkbeta and pkcdelta on serine residues ser132 and ser60, respectively, which interferes with its binding to ttp and hence the retention of ttp in the cytoplasm.

SIGNOR-138608

Q96AC1

P12931

2

binding

up-regulates activity

0.37

Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration.

SIGNOR-266101

P01106

P52789

1

transcriptional regulation

up-regulates quantity

0.37

Here, using the P493-6 Burkitt's lymphoma model with an inducible MYC, we demonstrate that HIF-1 cooperates with dysregulated c-Myc to promote glycolysis by induction of hexokinase 2, which catalyzes the first step of glycolysis, and pyruvate dehydrogenase kinase 1, which inactivates pyruvate dehydrogenase and diminishes mitochondrial respiration.

SIGNOR-259986

Q9NT99

P78352

1

binding

up-regulates activity

0.37

A possible function for the NGL–PSD-95 interaction is to couple trans-synaptic adhesion events to the recruitment of PSD-95 and other PSD-95-associated postsynaptic proteins. PSD-95 and liprin-α may be key synaptic scaffolding proteins that couple trans-synaptic adhesions to the assembly of synaptic proteins/vesicles

SIGNOR-264052

P16220

P01189

1

transcriptional regulation

up-regulates quantity by expression

0.37

Transcriptional activation of the proopiomelanocortin gene by cyclic AMP-responsive element binding protein|Further, expression of a dominant inhibitory mutant of CREB reduced cAMP stimulated transcription of the full length POMC promoter and the PTRE.

SIGNOR-268620

Q99750

P13349

1

binding

down-regulates activity

0.37

We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals.

SIGNOR-240433

P68400

Q00613

1

phosphorylation

up-regulates activity

0.37

Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2.

SIGNOR-250898

P19784

Q13144

1

phosphorylation

up-regulates activity

0.37

Two conserved sites (Ser712/713) are phosphorylated by casein kinase 2. They lie at the extreme C-terminus and are required for the interaction of eIF2Bepsilon with its substrate, eIF2, in vivo and for eIF2B activity in vitro.

SIGNOR-250990

P10398

Q15796

1

phosphorylation

down-regulates quantity by destabilization

0.37

Araf promotes Smad2 linker phosphorylation through S253.|In this study, we demonstrate that Araf can directly bind to and phosphorylate the linker of Smad2, leading to degradation of activated Smad2.

SIGNOR-279391

P04150

P41235

1

transcriptional regulation

up-regulates quantity by expression

0.37

Electrophoretic mobility shift, chromatin immunoprecipitation (ChIP), and streptavidin DNA binding assays revealed that DEX increased binding of HNF4alpha to the HNF4-RE and that an interaction of GR and HNF4alpha occurred at this site.

SIGNOR-251684

P35637

Q16637

1

relocalization

up-regulates activity

0.37

Here, we report that FUS associates with the SMN complex, mediated by U1 snRNP and by direct interactions between FUS and SMN.|The FUS IP and pulldown revealed that FUS also associates with components of the SMN complex, including SMN and Gemins 4 and 6 |Remarkably, the number of SMN-stained nuclear bodies was dramatically reduced in the FUS knockdown cells

SIGNOR-262107

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

P80370

P02751

1

binding

up-regulates

0.37

We show a direct interaction of pref-1 and fibronectin via the pref-1 juxtamembrane domain and fibronectin c-terminal domain

SIGNOR-165347

O00165

P16615

1

binding

down-regulates quantity by destabilization

0.37

The anti-apoptotic protein HAX-1 interacts with SERCA2 and regulates its protein levels to promote cell survival.|Importantly, HAX-1 overexpression was associated with down-regulation of SERCA2 expression levels, resulting in significant reduction of apparent ER Ca(2+) levels.

SIGNOR-262052

P06493

P49459

1

phosphorylation

up-regulates

0.37

Hhr6a is phosphorylated in vitro by cdk-1 and -2 on ser120, a residue conserved in all hhr6a homologues, resulting in a 4-fold increase in its ubiquitin-conjugating activity.

SIGNOR-116504

Q00987

Q9NXV6

1

ubiquitination

down-regulates

0.37

Carf interacts with hdm2 and is ubiquitinated and negatively regulated by hdm2 by proteasome-dependent degradation.

SIGNOR-160974

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

Q9HCI7

P04637

1

ubiquitination

down-regulates activity

0.37

Here we describe MSL2, a novel E3 ligase for p53 that promotes ubiquitin-dependent cytoplasmic p53 localization. Unlike Mdm2 or most other p53 E3 ligases, MSL2-mediated p53 ubiquitination does not affect the stability of p53. Moreover, the MSL2-mediated effect on p53 is Mdm2-independent. Thus, our study identifies an important ubiquitin-ligase for modulating p53 subcellular localization. MSL2 ubiquitination of p53 is required for p53 cytoplasmic localization.

SIGNOR-271774

Q9NZS9

Q14790

1

binding

down-regulates

0.37

We also demonstrate that the mitochondrial protein bar, which has been shown to simultaneously bind caspase-8 and bcl-2

SIGNOR-112585

P12931

Q96AC1

2

phosphorylation

up-regulates activity

0.37

Here we report that Src binds to and phosphorylates Kindlin-2 at Y193. Reciprocally, Kindlin-2-Y193 phosphorylation activates and maintains Src kinase activity. Kindlin-2-Y193 phosphorylation is also involved in its binding capacity with Migfilin and the recruitment of Migfilin to the focal adhesions. Functionally, we demonstrate that Kindlin-2-Y193 phosphorylation regulates Kindlin-2-mediated cell spreading and migration.

SIGNOR-266100

Q05513

P41594

1

phosphorylation

up-regulates activity

0.37

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-249284

P18146

Q9Y251

1

transcriptional regulation

up-regulates quantity by expression

0.37

Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer.

SIGNOR-254267

Q9UHD2

Q99558

1

phosphorylation

down-regulates quantity by destabilization

0.37

TBK1 induces NIK phosphorylation and degradation.

SIGNOR-279767

Q13490

Q9Y385

1

ubiquitination

down-regulates quantity by destabilization

0.37

We also found that ubiquitin-ligase (E3), c-IAP1 preferentially interacts with phosphorylated Ube2j1. Moreover, we noticed that phosphorylated Ube2j1 is rapidly degraded by the proteasome during ER stress cell recovery. Taken together, these data suggest that Ube2j1 and its phosphorylation is important for transient ER stress cell recovery and the phosphorylated Ube2j1 is degraded by the proteasome.

SIGNOR-263092

P48729

Q9UKV8

1

phosphorylation

down-regulates activity

0.369

Our experiments demonstrated that target engagement by AGO2 stimulates its hierarchical, multi-site phosphorylation by CSNK1A1 on a series of highly conserved residues (S824-S834).Although this impairs target binding, dephosphorylation by ANKRD52-PPP6C allows AGO2 to engage new targets. Inactivation of this cycle strongly inhibits global miRNA-mediated repression.

SIGNOR-276510

P07333

P16885

1

null

up-regulates

0.369

Studies with multipotent precursor cell lines (Fig. 4A) indicate that CSF-1R Tyr-807 and Tyr-721 promote macrophage differentiation via the PLC-Œ≥2 pathway

SIGNOR-255570

P24941

Q01167

1

phosphorylation

up-regulates

0.369

We have mapped two cdk phosphorylation sites, serines 368 and 423, which play a role in defining foxk2 function through regulating its stability and its activity as a transcriptional repressor protein. These two cdk sites appear vital for foxk2 function because expression of a mutant lacking these sites cannot be tolerated and causes apoptosis.

SIGNOR-167834

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

Q9H2P0

Q9GZQ8

1

binding

up-regulates activity

0.369

Here, we show for the first time that hippocampal ADNP deficiency paralleled reduced beclin1 expression which, in turn, parallels increased tauopathy and cell death. We now show that ADNP directly interacts with LC3B, implicating the requirement of a healthy ADNP system for the apoptotic/autophagy processes.

SIGNOR-266759

P29376

P22681

1

phosphorylation

up-regulates

0.369

Although c-cbl is found to be phosphorylated by ltk and therefore is a second candidate linking ltk with the pi3-kinase pathway along with irs-1, we found that the p85 subunit of pi3 kinase directly binds to tyrosine 753 of ltk, which is located within a yxxm motif, a consensus binding amino acid sequence for the sh2 domain of p85.

SIGNOR-49528

O00327

Q9UJ55

1

binding

down-regulates activity

0.369

Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.

SIGNOR-253517

Q76NI1

P11137

1

phosphorylation

up-regulates activity

0.369

V-KIND enhances Thr phosphorylation of MAP2.

SIGNOR-278950

P31749

P15559

1

phosphorylation

down-regulates quantity by destabilization

0.369

Akt phosphorylates NQO1 on S40 and T128 residues. Here we show that Akt phosphorylates NQO1 at T128 residues and triggers its polyubiquitination and proteasomal degradation, abrogating its antioxidative effects in PD. Akt binds NQO1 in a phosphorylation-dependent manner. Interestingly, Akt, but not PINK1, provokes NQO1 phosphorylation and polyubiquitination with Parkin as an E3 ligase.

SIGNOR-276868

Q9UQM7

P11831

1

phosphorylation

up-regulates activity

0.369

Skeletal muscle CaMKII enriches in nuclei and phosphorylates myogenic factor SRF at multiple sites. | Microsequencing of these phosphorylated peptides identified that both Ser-103 and a novel residue, Thr-160 in the MADS box of SRF, were sites of phosphorylation. | The location of Thr-160 in the 3-D structure of SRF suggests that its phosphorylation by nuclear CaMKII may directly influence DNA binding of SRF and other MADS box factors.

SIGNOR-250639

P28482

P42702

1

phosphorylation

down-regulates

0.369

Indeed, phosphorylation of the cytoplasmic domain of the low-affinity lif receptor alpha-subunit (lifr) in mono q-fractionated, lif-stimulated 3t3-l1 extracts occurred only in those fractions containing activated mapk;ser-1044 served as the major phosphorylation site in the human lifr for mapk both in agonist-stimulated 3t3-l1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro

SIGNOR-32753

Q00526

Q14934

1

phosphorylation

up-regulates activity

0.369

CDK3 enhances the transactivation and transcription activity of NFAT3.|NFAT3 can be phosphorylated by CDK3 at Ser259, which is critical for its transactivation activity and cell transformation.

SIGNOR-278511

Q9H4B4

P05412

1

phosphorylation

up-regulates

0.369

Stress-induced c-jun activation mediated by polo-like kinase 3 in corneal epithelial cells. Hypoxia/reoxygenation activated plk3 in hce cells to directly phosphorylate c-jun proteins at phosphorylation sites ser-63 and ser-73, and to increase dna binding activity of c-jun.

SIGNOR-157721

O14733

P35568

1

phosphorylation

down-regulates activity

0.369

Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signalInsulin increased the phosphorylation of Ser312, Ser616, Ser636, Ser892, Ser1101, and Ser1223 Ser312 can be phosphorylated by kinases, such as c-jun NH2-terminal kinase and inhibitor of _B kinase

SIGNOR-217920

P45983

Q96P20

1

phosphorylation

up-regulates activity

0.369

Ethanol induced JNK1 phosphorylation activated the NLRP3 inflammasome that induced caspase-1 dependent mitophagy inhibition, thereby exacerbating ROS accumulation and causing cell death.|However, recent studies suggested that Ser 194 phosphorylation of NLRP3 was essential for the control of inflammasome activation and that JNK1 directly phosphorylates NLRP3, which stimulates the self-association and oligomerization of NLRP3 [ xref , xref ].

SIGNOR-280034

Q15418

Q15653

1

phosphorylation

down-regulates quantity by destabilization

0.369

By using recombinant wild-type and mutant IkappaBbeta proteins, both active ERK2 and RSK1 were found to directly phosphorylate IkappaBbeta, but only active RSK1 phosphorylated IkappaBbeta on Ser19 and Ser23, two sites known to mediate the subsequent ubiquitination and degradation.

SIGNOR-280114

P28482

P68400

1

phosphorylation

up-regulates

0.369

Erk2, which is activated by egfr signaling, directly binds to ck2alpha via the erk2 docking groove and phosphorylates ck2alpha primarily at t360/s362, subsequently enhancing ck2alpha activity

SIGNOR-161855

P51812

Q14790

1

phosphorylation

down-regulates quantity by destabilization

0.369

The ribosomal S6 kinase 2 (RSK2) is a member of the p90 ribosomal S6 kinase (p90RSK) family of proteins and plays a critical role in proliferation, cell cycle, and cell transformation. Here, we report that RSK2 phosphorylates caspase-8, and Thr-263 was identified as a novel caspase-8 phosphorylation site. In addition, we showed that EGF induces caspase-8 ubiquitination and degradation through the proteasome pathway, and phosphorylation of Thr-263 is associated with caspase-8 stability.

SIGNOR-272997

Q9H4M3

P38398

1

binding

down-regulates quantity by destabilization

0.369

The F-box protein FBXO44 mediates BRCA1 ubiquitination and degradation. The Skp1-Cul1-F-box-protein44 (SCF(FBXO44)) complex ubiquitinates full-length BRCA1 in vitro.

SIGNOR-272037

Q12913

P19174

1

dephosphorylation

down-regulates

0.369

Cd148 can dephosphorylate lat and plc?1 In vitro. / plc?1 Undergoes inducible tyrosine phosphorylation following tcr stimulation (46), and this phosphorylation is required to stimulate its catalytic activity

SIGNOR-105790

Q86Y07

Q13469

1

phosphorylation

up-regulates

0.369

We demonstrate that vrk2 directly interacts and phosphorylates nfat1 in ser-32 within its n-terminal transactivation domain.

SIGNOR-199263

Q99801

Q13547

1

binding

down-regulates activity

0.369

NKX3.1 also binds HDAC1 and releases p53 from p53-MDM2-HDAC1 complex, promoting p53 acetylation and activity.

SIGNOR-251549

P53355

Q13526

1

phosphorylation

down-regulates activity

0.369

DAPK1 inhibits Pin1 nuclear localization and cellular function.|DAPK1 interacts with and phosphorylates Pin1 on Ser71 in vitro and in vivo.

SIGNOR-278160

Q9UDY2

O00192

1

relocalization

down-regulates activity

0.369

We identified ARVCF as a binding partner of ZO-1 and ZO-2 and characterized the role of PDZ-domain proteins in plasma membrane and nuclear localization of ARVCF. ZO-2, in contrast, relocated to the nucleus with ARVCF, and, given the interaction between the ZO-2 PDZ domains and ARVCF, raised the possibility that ZO-2 may play a role in nuclear localization of ARVCF. Such a role for ZO-2 is indeed supported by the ability of the ZO-2 PDZ domain to efficiently relocate ARVCF from the plasma membrane to the nucleus in a process that required the ability of the two proteins to interact and the presence of a functional NLS in the ZO-2 PDZ domains. Thus, ZO-2 could be involved in nuclear translocation and/or retention of ARVCF and play a role in regulating postulated functions of ARVCF in gene expression

SIGNOR-252122

P28482

Q9Y463

1

phosphorylation

up-regulates activity

0.369

S421 resides within a Ser-Pro phosphoacceptor motif that is typical for ERK1/2 and recombinant ERK2 phosphorylated DYRK1B at S421 in vitro.

SIGNOR-276937

Q13884

P53778

1

binding

down-regulates

0.368

Basal localization of the p38g/p-Carm1 complex in muscle stem cells occurs via binding to the dystrophin-glycoprotein complex (DGC) through b1-syntrophin. In dystrophin-deficient muscle stem cells undergoing asymmetric division, p38g/b1-syntrophin interactions are abrogated, resulting in enhanced Carm1 phosphorylation

SIGNOR-255901

Q05513

P31946

1

phosphorylation

down-regulates activity

0.368

Our results with the 14-3-3 mutants indirectly imply a new phosphorylation site, 130Ser (and to a lesser extent 141Thr), in 14-3-3b that regulates the association}dissociation of 14-3-3b and PKC-f.

SIGNOR-249035

P28482

P12036

1

phosphorylation

up-regulates activity

0.368

The fraction containing Erk2, as well as bacterially expressed Erk1 and Erk2, phosphorylated all types of KSP motifs in peptides (KSPXK, KSPXXK, KSPXXXK, and KSPXXXXK) derived from NF-M and NF-H. They also phosphorylated an expressed 24 KSPXXXK repeat NF-H polypeptide, an expressed NF-H as well as dephosphorylated native rat NF-H, and NF-M proteins with accompanying decreases in their respective electrophoretic mobilities. |Our data on primary hippocampal cells also showed an inhibition of neurite outgrowth by the drug that was accompanied by inhibition of MAP, NF-H, and NF-M phosphorylation.

SIGNOR-249424

P06493

O00418

1

phosphorylation

down-regulates

0.368

Phosphorylation at ser359 inhibits eef2k activity even at high calcium concentrations. we demonstrate that cdc2 contributes to controlling eef2 phosphorylation in cells. inactivation of eef2k by cdc2 may serve to keep eef2 active during mitosis

SIGNOR-177982

P46934

Q96GG9

1

monoubiquitination

up-regulates quantity

0.368

Here we revealed a previously unknown mechanism that regulates hDCNL1. In cultured mammalian cells ectopically expressed hDCNL1 was mono-ubiquitinated predominantly at K143, K149, and K171. Using a classical chromatographic purification strategy, we identified Nedd4-1 as an E3 ligase that can catalyze mono-ubiquitination of hDCNL1 in a reconstituted ubiquitination system.Taken together, these results suggest a mono-ubiquitination-mediated mechanism that governs nuclear-cytoplasmic trafficking of hDCNL1,

SIGNOR-272719

Q13535

Q92900

1

phosphorylation

up-regulates activity

0.368

Phosphorylation of UPF1 by the PIKKs SMG1, ATM and ATR is stimulated in response to DNA damage.

SIGNOR-278911

P49840

Q13144

1

phosphorylation

down-regulates activity

0.368

We identify multiple phosphorylation sites in the largest, catalytic, subunit (epsilon) of mammalian eIF2B. Glycogen synthase kinase 3 (GSK3) is responsible for phosphorylating Ser535. This regulatory phosphorylation event requires both the fourth site (Ser539) and a distal region, which acts to recruit GSK3 to eIF2Bepsilon in vivo. eIF2Bϵ from mammals or insects is a substrate for glycogen synthase kinase 3 (GSK3), and this inhibits the activity of eIF2B

SIGNOR-251215

Q13547

O43524

1

deacetylation

up-regulates activity

0.368

The ability of HDAC1 to cause muscle atrophy required its deacetylase activity and was linked to the induction of several atrophy genes by HDAC1, including atrogin-1, which required deacetylation of FoxO3a

SIGNOR-256486

Q7L7X3

Q13043

1

phosphorylation

up-regulates

0.368

In addition, the thousand-and-one (tao) amino acids kinase or taok13 has been shown to directly phosphorylate and activate hpo or mst1/2.

SIGNOR-201324

Q16539

Q6STE5

1

phosphorylation

up-regulates activity

0.368

P38 phosphorylates the baf60 subunit of the swi-snf chromatin remodelling complex, and p38 recruits this complex to differentiation-specific loci.

SIGNOR-176557

P45983

Q9H211

1

phosphorylation

up-regulates quantity by stabilization

0.368

We discovered that human Cdt1, an essential origin licensing protein whose activity must be restricted to G(1) phase, is a substrate of the stress-activated mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). These MAP kinases phosphorylate Cdt1 both during unperturbed G(2) phase and during an acute stress response. Phosphorylation renders Cdt1 resistant to ubiquitin-mediated degradation during S phase and after DNA damage by blocking Cdt1 binding to the Cul4 adaptor, Cdt2.

SIGNOR-276361

P29350

P08922

1

dephosphorylation

down-regulates

0.368

Overexpression of shp-1 results in ros dephosphorylation and effectively downregulates ros-dependent proliferation and transformation. We propose that shp-1 is an important downstream regulator of ros signaling.

SIGNOR-105922

O00408

P17612

1

binding

down-regulates activity

0.368

We show that caffeine, by inhibiting PDE2, enhances PKA phosphorylation leading to mitochondrial NCLX activation, thereby reducing neuronal excitotoxicity and enhancing learning in mice.

SIGNOR-275730

O94889

O14965

1

binding

up-regulates activity

0.368

We identify Aurora-A as a KLHL18-interacting partner. Overexpression of KLHL18 and CUL3 promotes Aurora-A ubiquitylation in vivo, and the CUL3-KLHL18-ROC1 ligase ubiquitylates Aurora-A in vitro. Our study reveals that the CUL3-KLHL18 ligase is required for timely entry into mitosis, as well as for the activation of Aurora-A at centrosomes.We also noticed that overexpression of both CUL3 and KLHL18 stimulated mono-ubiquitylation of Aurora-A as well (Fig. 8A,B).

SIGNOR-272021

P68400

P45973

1

phosphorylation

up-regulates

0.368

Hp1_ was multiply phosphorylated at n-terminal serine residues (s11-14) in human and mouse cells and that this phosphorylation enhanced hp1_'s affinity for h3k9me. Unphosphorylatable mutant hp1_ exhibited severe heterochromatin localization defects in vivo, and its prolonged expression led to increased chromosomal instability.

SIGNOR-171707

P06493

Q9Y6Q9

1

phosphorylation

down-regulates

0.368

We demonstrate that aib1 is phosphorylated on ser728 and ser867 by cdk1/cyclin b at the onset of mitosis and remains phosphorylated until exit from m phase.

SIGNOR-195233

Q9ULU8

P60880

1

binding

up-regulates activity

0.368

CAPS interacted independently with either syntaxin-1 or SNAP-25 suggesting that CAPS might promote QaQbc-SNARE heterodimer formation. CAPS binding to syntaxin-1 was mediated by the membrane-proximal C-terminal SNARE motif (H3) and membrane linker domain sequences of syntaxin-1

SIGNOR-264338

P10747

P48736

1

binding

up-regulates

0.368

Cd28 can bind directly to pi3k by a well-characterized ymnm binding motif in its cytoplasmic domain.

SIGNOR-159322

P17612

P07101

1

phosphorylation

up-regulates activity

0.368

HTH1 was phosphorylated at Ser40 by PKA. Tyrosine hydroxylase (TH) has been reported to require binding of 14-3-3 proteins for optimal activation by phosphorylation. phosphorylationof hTH1‚4 at Ser40, to a stoichiometry of up to 1.0 molphosphate per mol TH subunit, dramatically increases their binding to 14-3-3 proteins.

SIGNOR-250061

Q99873

P62633

1

methylation

down-regulates

0.368

Cnbp interacts with protein arginine methyltransferase prmt1 / r25 or r27 appear to be the major methylation sites in cnbp /arginine methylation of cnbp impedes rna binding

SIGNOR-204958

P27361

O15525

1

phosphorylation

up-regulates quantity

0.368

By contrast, MAFG-S124A was not phosphorylated, indicating that ERK1 phosphorylates MAFG at S124.|Notably, cotransfection of ERK1 increased total levels of wild-type MAFG and MAFG-T3A but not MAFG-S124A, indicating that phosphorylation increased MAFG stability.

SIGNOR-280027

Q8WTV0

P12931

1

binding

up-regulates activity

0.368

Importantly, coimmunoprecipitation of SR-BI and Src demonstrated that the two proteins are directly associated in WT macrophages (Fig. 7B), suggesting that SR-BI plays a direct role in activation of Src in macrophages.

SIGNOR-260314

P07332

P11274

1

phosphorylation

down-regulates activity

0.368

In the present study, we demonstrate that BCR Tyr-246 and at least one of the closely spaced tyrosine residues, Tyr-279, Tyr-283, and Tyr-289 (3Y cluster), are phosphorylated by FES both in vitro and in 32Pi-labeled cells. Co-expression of BCR and FES in human 293T cells stimulated the tyrosine autophosphorylation of FES. By contrast, tyrosine phosphorylation of BCR by FES suppressed BCR serine/threonine kinase activity toward the 14-3-3 protein and BCR substrate, BAP-1.

SIGNOR-251137

P39880

Q96FE7

1

transcriptional regulation

down-regulates quantity by repression

0.368

We demonstrate that CUX1 deficiency activates phosphoinositide 3-kinase (PI3K) signaling through direct transcriptional downregulation of the PI3K inhibitor PIK3IP1 (phosphoinositide-3-kinase interacting protein 1), leading to increased tumor growth and susceptibility to PI3K-AKT inhibition.

SIGNOR-260072

Q14790

P49768

1

cleavage

up-regulates activity

0.368

Remarkably, the caspases acting on PS1 could be subdivided in two groups. One group, containing caspase-8, -6 and -11, cleaved PS1 after residues ENDD329 and to a lesser extent after residues AQRD341. A second group consisting of caspase-3, -7 and -1 acted uniquely on AQRD341. Importantly, these two cleavage sites were also recognized by caspases in the C-terminal PS1 fragment produced by constitutive proteolysis.

SIGNOR-261760

Q92949

Q9UI46

1

transcriptional regulation

up-regulates quantity by expression

0.368

FOXJ1 expression in basal cells induced the expression of a panel of cilia-associated genes, including centrin 2 (CETN2); dynein, axonemal, heavy chain 11 (DNAH11); dynein, axonemal, intermediate chain 1 (DNAI1); dynein, axonemal, light intermediate chain 1 (DNALI1); EF-hand domain, C-terminal, containing 1 (EFHC1); sperm associated antigen 6 (SPAG6); tektin 1 (TEKT1), TEKT2 and tubulin, alpha 1a (TUBA1A; Figure 3C and Additional file 2: Table S1).

SIGNOR-266932

Q96GD4

P25490

1

phosphorylation

up-regulates

0.368

Aurora b kinase phosphorylates yy1 on serine 184 and to a lesser extent serine 180 at the g2/m stage of the cell cycle (fig. 7). We show that yy1 is rapidly dephosphorylated as the cells exit mitosis, likely by pp1. Also, our data indicates that phosphorylation at serine 180 and serine 184 can affect the dna binding activity of yy1

SIGNOR-200079

Q05655

P00533

1

phosphorylation

down-regulates activity

0.368

These data indicate that activation of protein kinase C and subsequent phosphorylation of the EGF receptor at T654 lead to rapid physiological attenuation of EGF receptor signaling.

SIGNOR-248858

P49841

Q13887

1

phosphorylation

down-regulates

0.368

Stability of the klf5 is mediated by proteasomal degradation via phosphorylation by glycogen synthase kinase 3_ (gsk3_) and recognition by f-box and wd repeat domain-containing 7 (fbw7) of a phosphodegron sequence surrounding serine 303 in klf5

SIGNOR-203627

O43474

P11831

1

binding

down-regulates

0.368

Klf4 antagonizes contractile gene expression through diverse mechanisms including (i) inhibiting the binding of srf-myocd or srf-mrtfs to the carg box by direct association with srf.

SIGNOR-174258

P51812

P25963

1

phosphorylation

down-regulates quantity by destabilization

0.368

Here, we show that RSK2 is activated by treatment with tumor necrosis factor-alpha (TNF-alpha) and directly phosphorylates IkappaBalpha at Ser 32, leading to IkappaBalpha degradation.

SIGNOR-279108

P12931

P15498

1

phosphorylation

up-regulates activity

0.368

These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module.|These interactions are required for SRC-induced tyrosine phosphorylation and activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module ( xref ).

SIGNOR-279124

P28482

Q05469

1

phosphorylation

up-regulates activity

0.368

Thus, activation of the ERK pathway appears to be able to regulate adipocyte lipolysis by phosphorylating HSL on Ser(600) and increasing the activity of HSL.

SIGNOR-249413

Q00535

O14939

1

phosphorylation

up-regulates activity

0.368

In this study, we suggest that the phosphorylation and activation of PLD2 by cyclin-dependent kinase 5 (Cdk5) is critical for EGF-dependent insulin secretion.|We determined that Cdk5 phosphorylates PLD2 at Ser 134 of PLD2 and that this phosphorylation was suggested to be important for EGF-dependent insulin secretion.

SIGNOR-278395

P06493

P12830

1

phosphorylation

up-regulates activity

0.368

We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.|We show that adequate accumulation of Cin8 and Kip1 requires inactivation of the anaphase-promoting complex-activator Cdh1 through sequential phosphorylation by Cdk1 and polo kinase.

SIGNOR-280204

P31749

P23396

1

phosphorylation

up-regulates activity

0.368

Here, we show that human RPS3 is a physiological target of Akt kinase and a novel mediator of neuronal apoptosis. NGF stimulation resulted in phosphorylation of threonine 70 of RPS3 by Akt, and this phosphorylation was required for Akt binding to RPS3.our experiment demonstrated that Akt up-regulates the endonuclease activity of RPS3 via phosphorylation and led us to believe that Akt phosphorylation of RPS3 after DNA damage is an antiapoptotic signal or a molecular switch that extends the life of a cell after DNA damage.

SIGNOR-259815