GleghornLab/Signor_processed · Datasets at Hugging Face

IdA stringlengths 6 21	IdB stringlengths 6 21	mechanism stringclasses 40 values	effect stringclasses 10 values	score float64 0.1 0.99 ⌀	sentence stringlengths 10 1.63k ⌀	signor_id stringlengths 12 14
P27986	P35813	dephosphorylation	up-regulates activity	0.324	Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes\|PP2Cα dephosphorylates the p85 subunit of PI3K, and dephosphorylation of the p85 subunit of PI3K at Ser608 increases its activity	SIGNOR-248489
Q00987	Q5XUX0	binding	down-regulates quantity by destabilization	0.324	FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2.	SIGNOR-277380
O14746	P06493	phosphorylation	up-regulates activity	0.324	Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1.These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.	SIGNOR-277517
O60885	O60674	phosphorylation	up-regulates quantity by stabilization	0.324	JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization.	SIGNOR-277312
Q16637	Q86YT6	ubiquitination	down-regulates quantity by destabilization	0.324	The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein	SIGNOR-253112
P10636	P20807	cleavage	down-regulates activity	0.324	Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains	SIGNOR-251605
O43516	Q04759	phosphorylation	up-regulates activity	0.324	TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation. \| These results suggest that phosphorylation at S488 disrupts WIP binding to WASP.	SIGNOR-249181
Q16665	P48730	phosphorylation	down-regulates	0.324	In this work, we investigate the phosphorylation of the n-terminal heterodimerization (pas) domain of hif-1alpha and identify ser247 as a major site of in vitro modification by casein kinase 1delta (ck1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of hif-1alpha	SIGNOR-167476
Q13224	P68400	phosphorylation	down-regulates	0.324	Here we show that casein kinase ii (ck2) phosphorylates the serine residue (ser1480) within the c-terminal pdz ligand (iesdv) of the nr2b subunit of nmdar in vitro and in vivo. Phosphorylation of ser1480 disrupts the interaction of nr2b with the pdz domains of psd-95 and sap102 and decreases surface nr2b expression in neurons.	SIGNOR-130336
Q16658	Q05655	phosphorylation	down-regulates activity	0.324	Phosphorylation of human fascin inhibits its actin binding and bundling activities.	SIGNOR-248944
P49840	P05129	phosphorylation	down-regulates	0.324	Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.	SIGNOR-115726
P04275	O00327	transcriptional regulation	down-regulates quantity by repression	0.324	We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype.	SIGNOR-253704
Q08881	Q06124	dephosphorylation	down-regulates activity	0.324	Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions.	SIGNOR-277174
Q9BR76	P17252	phosphorylation	down-regulates	0.324	We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.	SIGNOR-138733
Q96GD4	O96017	phosphorylation	up-regulates activity	0.324	Because Chk1 and Chk2 can share substrates ( ), we investigated whether Chk2 phosphorylates Aurora B-B-serine 331 in nocodazole.\|In addition, Chk2 promotes proper chromosome alignment through Aurora B-B-serine 331 phosphorylation.	SIGNOR-278906
O75626	O75925	sumoylation	up-regulates	0.324	Blimp_1 is subjected to pias1_mediated sumoylation at lysine 816 / it appears that sumo_modified blimp_1 is a more potent transcriptional repressor.	SIGNOR-197265
P26010	Q99704	binding	down-regulates activity	0.324	Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation	SIGNOR-257695
Q9UIF3	Q92949	transcriptional regulation	up-regulates quantity by expression	0.324	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-266937
P46531	O00505	relocalization	up-regulates	0.324	Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.	SIGNOR-165280
P25024	Q00765	binding	up-regulates activity	0.324	In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses.	SIGNOR-261366
Q14152	Q9Y6E2	binding	up-regulates activity	0.324	BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro	SIGNOR-261221
Q08050	P12931	phosphorylation	up-regulates activity	0.324	Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2.	SIGNOR-279117
P05412	Q9UBF6	ubiquitination	down-regulates activity	0.324	SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.	SIGNOR-271452
Q86UR1	P17612	phosphorylation	down-regulates	0.324	We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I	SIGNOR-163663
Q9UBP6	Q15418	phosphorylation	down-regulates	0.324	Pkb and ribosomal s6 kinase (rsk) both phosphorylated mettl1 at ser27 in vitro.	SIGNOR-135948
O60936	P68400	phosphorylation	up-regulates activity	0.324	Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.	SIGNOR-262837
Q9NQ66	P63092	binding	up-regulates activity	0.324	The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase c (plc) are activated by g protein alpha q and beta gamma subunits.	SIGNOR-265066
O43597	Q15139	phosphorylation	down-regulates quantity by destabilization	0.324	PKD negatively affects the stability of Spry2 WT but not of mutant Spry2 S112A.\|Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein.	SIGNOR-280091
O43186	P08047	binding	up-regulates activity	0.324	Zinc finger DNA-binding domains of both Sp1 and Sp3 interact with Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.	SIGNOR-225336
Q8N137	P53350	phosphorylation	up-regulates activity	0.324	However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].\|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation.	SIGNOR-279551
Q14449	P49841	phosphorylation	down-regulates activity	0.323	Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor\| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.	SIGNOR-264867
P41970	P45984	phosphorylation	down-regulates activity	0.323	JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.	SIGNOR-250138
O96019	P50750	phosphorylation	up-regulates activity	0.323	Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro.	SIGNOR-279689
P08151	P28482	phosphorylation	up-regulates activity	0.323	We conclude that multisite phosphorylation of GLI1 by ERK2 or other MAP kinases weakens GLI1-SUFU binding, thereby facilitating GLI1 activation and contributing to both physiological and pathological crosstalk.	SIGNOR-277601
P31749	P07949	phosphorylation	up-regulates	0.323	The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity	SIGNOR-252619
Q15366	P27361	phosphorylation	up-regulates quantity by stabilization	0.323	We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).	SIGNOR-262916
P24071	P67775	dephosphorylation	up-regulates activity	0.323	Furthermore, FcalphaRI activation is induced by protein phosphatase 2A (PP2A) after it dephosphorylates a single serine residue (S263) in the FcalphaRI intracellular tail	SIGNOR-264858
Q5JWF2	P43657	binding	up-regulates activity	0.323	LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa.	SIGNOR-278872
P51692	Q15788	binding	up-regulates	0.323	Ncoa-1/src-1 is an essential coactivator of stat5 that binds to the fdl motif in the alpha-helical region of the stat5 transactivation domain.	SIGNOR-100261
Q96GD4	Q7Z3K3	binding	up-regulates activity	0.323	POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis.	SIGNOR-264497
O60674	Q12913	dephosphorylation	down-regulates activity	0.323	These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.\|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation.	SIGNOR-277094
P10915	P09238	cleavage	down-regulates quantity by destabilization	0.323	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256332
Q9Y6I3	P06493	phosphorylation	down-regulates activity	0.323	Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.	SIGNOR-262723
P14210	P03952	cleavage	up-regulates activity	0.323	the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.	SIGNOR-256513
P08473	P68400	phosphorylation	down-regulates	0.323	The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten.	SIGNOR-168673
Q15717	O15111	phosphorylation	down-regulates quantity by destabilization	0.323	Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli.	SIGNOR-276422
P63092	Q96RI0	binding	up-regulates activity	0.323	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256772
P42262	P51608	transcriptional regulation	down-regulates quantity by repression	0.323	Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A.	SIGNOR-264684
P31269	O15550	transcriptional regulation	up-regulates quantity by expression	0.323	Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.	SIGNOR-260025
P41970	P45983	phosphorylation	down-regulates activity	0.323	JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.	SIGNOR-250139
P63092	P43657	binding	up-regulates activity	0.323	LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa.	SIGNOR-278873
Q12929	P27361	phosphorylation	down-regulates activity	0.323	We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation.	SIGNOR-263058
P63092	P47900	binding	up-regulates activity	0.323	Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. \| We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ‚â• -1.0.	SIGNOR-256800
P60953	Q9ULL1	guanine nucleotide exchange factor	up-regulates activity	0.323	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-260563
P10415	Q15173	dephosphorylation	down-regulates	0.323	Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.	SIGNOR-181559
P12830	Q12955	binding	up-regulates activity	0.323	Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton.	SIGNOR-266710
P22830	Q16236	transcriptional regulation	up-regulates quantity by expression	0.322	NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated.	SIGNOR-279865
Q13263	P62136	dephosphorylation	up-regulates activity	0.322	PP1\u03b1 dephosphorylates KAP1 at Ser 824 .	SIGNOR-277075
O43464	P31749	phosphorylation	down-regulates	0.322	Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212	SIGNOR-252500
P18031	P49760	phosphorylation	up-regulates activity	0.322	The clk family kinases, clk1 and clk2, phosphorylate and activate the tyrosine phosphatase, ptp-1b.\|Phosphorylation of PTP-1B at Ser(50) by CLK1 or CLK2 is responsible for its enzymatic activation.	SIGNOR-70603
Q02952	P06493	phosphorylation	up-regulates activity	0.322	Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis.	SIGNOR-271839
P35548	P05771	phosphorylation	up-regulates quantity	0.322	PKCbeta increased the level of overexpressed Msx2, but PKC alpha, delta and zeta did not have any significant effects.\|Thr135 and Thr141 in Msx2 can be phosphorylated by PKC\u03b2, and Thr135 is important for regulating the protein stability of Msx2 by PKCs.	SIGNOR-278982
P16284	P16591	phosphorylation	up-regulates activity	0.322	PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1.	SIGNOR-262866
Q9NRA8	P45983	phosphorylation	up-regulates	0.322	Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress.	SIGNOR-199004
P10915	P09237	cleavage	down-regulates quantity by destabilization	0.322	Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.	SIGNOR-256329
P22681	P17252	phosphorylation	down-regulates quantity	0.322	However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway.	SIGNOR-249056
Q04721	A0PJZ3	binding	up-regulates	0.322	We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.	SIGNOR-177717
Q14596	P49840	phosphorylation	down-regulates activity	0.322	The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation\|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.	SIGNOR-261794
Q93034	P17612	phosphorylation	up-regulates activity	0.322	Elimination of the S730 but not the T325 PKA phosphorylation site of VACM-1 resulted in a complete inhibition of the VACM-1 activity, thus suggesting a direct effect of PKA on the VACM-1 receptor.	SIGNOR-250352
Q15633	P23443	phosphorylation	up-regulates activity	0.322	We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.	SIGNOR-274068
P27986	Q9H0K1	phosphorylation	up-regulates activity	0.322	The Regulatory Subunit of PI3K Is a Direct Catalytic Target of SIK2. These data confirm that p85α is a direct catalytic substrate of SIK2 and that SIK2 S154 phosphorylation significantly increases the activity of the PI3K/AKT pathway in ovarian cancer cells.	SIGNOR-277269
P05787	Q05655	phosphorylation	up-regulates	0.322	The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC.	SIGNOR-260887
P19404	P12931	phosphorylation	up-regulates activity	0.322	Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.	SIGNOR-276419
P35580	Q14814	transcriptional regulation	up-regulates quantity by expression	0.322	Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation	SIGNOR-238766
Q8IXT1	Q9UNE7	ubiquitination	down-regulates quantity by destabilization	0.322	HSP70 recruits DDIAS to the CHIP E3 ligase, whereas CHIP promotes the ubiquitination of DDIAS.\|However, the findings clearly demonstrated that HSP70 was solely involved in CHIP mediated proteasomal degradation of DDIAS.	SIGNOR-278784
Q14498	P00519	phosphorylation	up-regulates activity	0.322	In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner.	SIGNOR-262609
Q9UD71	P49674	phosphorylation	up-regulates activity	0.322	CKIepsilon phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence.	SIGNOR-279701
Q05209	P17252	phosphorylation	down-regulates	0.322	Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate.	SIGNOR-27300
P20338	Q92597	binding	up-regulates	0.322	In this report evidence is provided that ndrg1 is a rab4a effector protein that localizes to perinuclear recycling/sorting vesicles in the trans golgi network by binding to phophatidylinositol 4-phosphate and is involved in recycling of e-cadherin. This is the first demonstration providing evidence that ndrg1 is a rab4a effector recruiting to recycling/sorting endosomes.	SIGNOR-157697
Q13362	O96017	phosphorylation	up-regulates	0.322	Found that chk2 associated with the b' regulatory subunit of protein phosphatase pp2a. In vitro kinase assays showed that b'gamma3 was a potent chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of pp2a.	SIGNOR-129255
Q9UQ13	P28482	phosphorylation	down-regulates quantity by destabilization	0.322	Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.	SIGNOR-277442
P07203	P42684	phosphorylation	up-regulates activity	0.322	GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.	SIGNOR-104328
Q09472	P20962	binding	up-regulates activity	0.322	Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.	SIGNOR-268461
Q07954	P01009	binding	up-regulates	0.322	In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp	SIGNOR-41180
Q8TEA8	O00311	phosphorylation	up-regulates activity	0.321	Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D).	SIGNOR-273967
P46937	P49336	phosphorylation	up-regulates activity	0.321	CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.	SIGNOR-277651
P28329	P05129	phosphorylation	up-regulates	0.321	We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.	SIGNOR-129320
Q99259	Q02156	phosphorylation	down-regulates activity	0.321	We have identified one specific phosphorylation site, threonine 91 (T91), in hGAD67 that can be phosphorylated by PKA using MALDI-TOF. Site-directed mutation of T91 to alanine abolished PKA-mediated phosphorylation and inhibition of GAD activity.	SIGNOR-249264
Q9BV73	Q9H0K1	phosphorylation	down-regulates	0.321	Here, we show that the salt inducible kinase 2 (sik2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, c-nap1, through s2392 phosphorylation	SIGNOR-167488
P04637	Q9BXM7	phosphorylation	up-regulates activity	0.321	Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.\|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria.	SIGNOR-278418
P49840	P24723	phosphorylation	down-regulates	0.321	Furthermore, several pkc isotypes phosphorylate gsk-3 in vitro and in vivo. in the presence of atp, several isoforms (?, ___, _, ?, And of pkc phosphorylated both gsk-3? At ser 21 and gsk-3_ at ser 9	SIGNOR-115730
Q15831	Q05513	phosphorylation	up-regulates	0.321	Here, we have identified s307 as a novel phosphorylation site in lkb1 and provide evidence that, in multiple cell types, phosphorylation of this site by protein kinase c ? (pkc-?) Induces nucleocytoplasmic transport of lkb1.	SIGNOR-185640
Q92993	Q16539	phosphorylation	up-regulates activity	0.321	We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158.	SIGNOR-278958
Q13886	P04150	transcriptional regulation	up-regulates quantity by expression	0.321	We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα	SIGNOR-256119
Q9HC29	P08238	binding	up-regulates quantity by stabilization	0.321	Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.	SIGNOR-252415
Q6UUV9	Q13233	phosphorylation	up-regulates	0.321	We report on the activation oftorc1through mekk1-mediated phosphorylation.	SIGNOR-180816
Q16143	P34947	phosphorylation	down-regulates activity	0.321	GRK5 prefers alpha-synuclein as a substrate. GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser118 practically abolishes Œ≤-synuclein phosphorylation by both GRK2 and GRK5	SIGNOR-251203
Q9Y281	Q15569	phosphorylation	down-regulates activity	0.321	Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin	SIGNOR-246719
Q9Y281	Q96S53	phosphorylation	down-regulates activity	0.321	Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin	SIGNOR-246711
P31749	P24666	dephosphorylation	down-regulates activity	0.321	Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.\|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3	SIGNOR-248455

P27986

P35813

0

dephosphorylation

up-regulates activity

0.324

Protein phosphatase-2C alpha as a positive regulator of insulin sensitivity through direct activation of phosphatidylinositol 3-kinase in 3T3-L1 adipocytes|PP2Cα dephosphorylates the p85 subunit of PI3K, and dephosphorylation of the p85 subunit of PI3K at Ser608 increases its activity

SIGNOR-248489

Q00987

Q5XUX0

0

binding

down-regulates quantity by destabilization

0.324

FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2.

SIGNOR-277380

O14746

P06493

0

phosphorylation

up-regulates activity

0.324

Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1.These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.

SIGNOR-277517

O60885

O60674

0

phosphorylation

up-regulates quantity by stabilization

0.324

JAK2 induces tyrosine phosphorylation of BRD4 at Y97/Y98, resulting in BRD4 stabilization.

SIGNOR-277312

Q16637

Q86YT6

0

ubiquitination

down-regulates quantity by destabilization

0.324

The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein

SIGNOR-253112

P10636

P20807

0

cleavage

down-regulates activity

0.324

Besides tau phosphorylation, calpain activation might play a role in tau-mediated neurodegeneration by inducing tau cleavage. In vitro studies have shown that both fetal and adult tau isoforms are rapidly proteolyzed by calpains

SIGNOR-251605

O43516

Q04759

0

phosphorylation

up-regulates activity

0.324

TCR engagement also causes PKCtheta-dependent phosphorylation of WIP, causing the disengagement of WASP from the WIP-WASP complex, thereby releasing it from WIP inhibition. These results suggest that the ZAP-70-CrkL-WIP pathway and PKCtheta link TCR to WASP activation. | These results suggest that phosphorylation at S488 disrupts WIP binding to WASP.

SIGNOR-249181

Q16665

P48730

0

phosphorylation

down-regulates

0.324

In this work, we investigate the phosphorylation of the n-terminal heterodimerization (pas) domain of hif-1alpha and identify ser247 as a major site of in vitro modification by casein kinase 1delta (ck1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of hif-1alpha

SIGNOR-167476

Q13224

P68400

0

phosphorylation

down-regulates

0.324

Here we show that casein kinase ii (ck2) phosphorylates the serine residue (ser1480) within the c-terminal pdz ligand (iesdv) of the nr2b subunit of nmdar in vitro and in vivo. Phosphorylation of ser1480 disrupts the interaction of nr2b with the pdz domains of psd-95 and sap102 and decreases surface nr2b expression in neurons.

SIGNOR-130336

Q16658

Q05655

0

phosphorylation

down-regulates activity

0.324

Phosphorylation of human fascin inhibits its actin binding and bundling activities.

SIGNOR-248944

P49840

P05129

0

phosphorylation

down-regulates

0.324

Convergence of multiple signaling cascades at glycogen synthase kinase 3: edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase c-dependent intracellular pathway.

SIGNOR-115726

P04275

O00327

0

transcriptional regulation

down-regulates quantity by repression

0.324

We also show that major circadian transcriptional regulators CLOCK and Bmal1 directly regulate the activity of vWF promoter and that lack of Bmal1 results in upregulation of vWF both at mRNA and protein level. Here we report a direct regulation of vWF expression in endothelial cells by biological clock gene Bmal1. This study establishes a mechanistic connection between Bmal1 and cardiovascular phenotype.

SIGNOR-253704

Q08881

Q06124

0

dephosphorylation

down-regulates activity

0.324

Using genetic and pharmacological approaches, we discovered that SHP2 dephosphorylates ITK specifically downstream of PD-1 and that this event was associated with PD-1 inhibitory cellular functions.

SIGNOR-277174

Q9BR76

P17252

0

phosphorylation

down-regulates

0.324

We have identified serine 2 (ser-2) on coronin 1b as the major residue phosphorylated by pkc in vivo.In this work, we show that coronin 1b interacts in vivo with the arp2/3 complex and that this interaction is inhibited by pkc phosphorylation.

SIGNOR-138733

Q96GD4

O96017

0

phosphorylation

up-regulates activity

0.324

Because Chk1 and Chk2 can share substrates ( ), we investigated whether Chk2 phosphorylates Aurora B-B-serine 331 in nocodazole.|In addition, Chk2 promotes proper chromosome alignment through Aurora B-B-serine 331 phosphorylation.

SIGNOR-278906

O75626

O75925

0

sumoylation

up-regulates

0.324

Blimp_1 is subjected to pias1_mediated sumoylation at lysine 816 / it appears that sumo_modified blimp_1 is a more potent transcriptional repressor.

SIGNOR-197265

P26010

Q99704

0

binding

down-regulates activity

0.324

Integrins also bind to many PTBdomain-containing proteins (Calderwood et al., 2003) – including Dok1 and integrincytoplasmic-domain-associated protein 1 (ICAP1) – and these can compete with talin for binding to integrin and so can impair activation

SIGNOR-257695

Q9UIF3

Q92949

0

transcriptional regulation

up-regulates quantity by expression

0.324

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-266937

P46531

O00505

0

relocalization

up-regulates

0.324

Nicd binds via one of its four potential nuclear localization signals to importins alfa3, alfa4, and alfa7.

SIGNOR-165280

P25024

Q00765

0

binding

up-regulates activity

0.324

In this study, we found that CXCR1 interacted with REEP5 and REEP6, but CXCR2 did not. Overexpression of REEP5 and REEP6 enhanced IL-8-stimulated cellular responses through CXCR1, whereas depletion of the proteins led to the downregulation of the responses.

SIGNOR-261366

Q14152

Q9Y6E2

0

binding

up-regulates activity

0.324

BZW2, as an evolutionary highly conserved protein, interacts with eIF2 and eIF3 and promotes ternary complex formation in vitro

SIGNOR-261221

Q08050

P12931

0

phosphorylation

up-regulates activity

0.324

Hence, c-Src-dependent phosphorylation of MPP2 could be part of a negative feedback loop within the circuitry that modulates c-Src activity by MPP2.

SIGNOR-279117

P05412

Q9UBF6

0

ubiquitination

down-regulates activity

0.324

SAG (Sensitive to Apoptosis Gene), also known as RBX2 (RING box protein 2), ROC2 (Regulator of Cullins 2), or RNF7 (RING Finger Protein 7), was originally cloned in our laboratory as a redox inducible antioxidant protein and later characterized as the second member of the RBX/ROC RING component of the SCF (SKP1-CUL-F-box Proteins) E3 ubiquitin ligase. by forming a complex with other components of the SCF E3 ligase, SAG promotes ubiquitination and degradation of a number of protein substrates, including c-JUN, DEPTOR, HIF-1α, IκBα, NF1, NOXA, p27, and procaspase-3, thus regulating various signaling pathways and biological processes.

SIGNOR-271452

Q86UR1

P17612

0

phosphorylation

down-regulates

0.324

We identified ser-282 as target of mapk and ser-172 as target of pkc and pka in vitro and in a transfected human embryonic kidney 293 (hek293) cell model using site directed mutagenesis and phosphopeptide mapping analysis. In hek293 cells, phosphorylation of these sites occurred at a basal level and down-regulated constitutive nox1 activity. I

SIGNOR-163663

Q9UBP6

Q15418

0

phosphorylation

down-regulates

0.324

Pkb and ribosomal s6 kinase (rsk) both phosphorylated mettl1 at ser27 in vitro.

SIGNOR-135948

O60936

P68400

0

phosphorylation

up-regulates activity

0.324

Phosphorylation of ARC at T149 Is Required for Its Antiapoptotic Effect. Here we report that the function of ARC is regulated by protein kinase CK2. ARC at threonine 149 is phosphorylated by CK2. This phosphorylation targets ARC to mitochondria. ARC is able to bind to caspase-8 only when it is localized to mitochondria but not to the cytoplasm.

SIGNOR-262837

Q9NQ66

P63092

0

binding

up-regulates activity

0.324

The beta- but not the gamma- and delta-type isozymes of inositol phospholipid-specific phospholipase c (plc) are activated by g protein alpha q and beta gamma subunits.

SIGNOR-265066

O43597

Q15139

0

phosphorylation

down-regulates quantity by destabilization

0.324

PKD negatively affects the stability of Spry2 WT but not of mutant Spry2 S112A.|Using in vitro and in vivo assays, we show that protein kinase D (PKD) phosphorylates Spry2 at serine 112 and interacts in vivo with the C-terminal half of this protein.

SIGNOR-280091

O43186

P08047

0

binding

up-regulates activity

0.324

Zinc finger DNA-binding domains of both Sp1 and Sp3 interact with Crx. Sp4 and Sp1 produce much higher levels of transcriptional activation when co-transfected with Crx, they may additionally act by directly increasing the rate of transcriptional initiation by the general transcriptional apparatus through their activation domains.

SIGNOR-225336

Q8N137

P53350

0

phosphorylation

up-regulates activity

0.324

However, unlike NEK2, PLK1 phosphorylation enhances the microtubule stabilizing activity of centrobin [22].|PLK1 phosphorylation of centrobin is critical for bipolar spindle formation.

SIGNOR-279551

Q14449

P49841

0

phosphorylation

down-regulates activity

0.323

Phosphorylation of clustered serine residues in the N-terminus of BPS domain negatively regulates formation of the complex between human Grb14 and insulin receptor| In vitro kinase assay using the motif-derived peptides showed that the serine residues located in N-terminal (Ser358, Ser362 and Ser366) and C-terminal (Ser419 and Ser423) regions of the BPS domain were phosphorylated by GSK-3.

SIGNOR-264867

P41970

P45984

0

phosphorylation

down-regulates activity

0.323

JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.

SIGNOR-250138

O96019

P50750

0

phosphorylation

up-regulates activity

0.323

Collectively, these results suggest that the cdk9 and Cyclin T complex more efficiently phosphorylates Baf53 in vitro.

SIGNOR-279689

P08151

P28482

0

phosphorylation

up-regulates activity

0.323

We conclude that multisite phosphorylation of GLI1 by ERK2 or other MAP kinases weakens GLI1-SUFU binding, thereby facilitating GLI1 activation and contributing to both physiological and pathological crosstalk.

SIGNOR-277601

P31749

P07949

0

phosphorylation

up-regulates

0.323

The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity

SIGNOR-252619

Q15366

P27361

0

phosphorylation

up-regulates quantity by stabilization

0.323

We also identified 4 hnRNP-E2 MAPKERK1/2 phosphorylation sites and demonstrated that hnRNP-E2 is a bona fide MAPKERK1/2 substrate and that MAPKERK1/2-dependent phosphorylation of hnRNP-E2 at these amino acid residues is essential for increased hnRNP-E2 expression in BCR/ABL-expressing cells. Serine/threonine to alanine substitution abolishes hnRNP-E2 phosphorylation and markedly decreases its stability in BCR/ABL-expressing myeloid precursors. Consistent with the existence of a BCR/ABL-MAPK pathway that posttranslationally regulates hnRNP-E2 expression, sequence analysis of hnRNP-E2 revealed the presence of 4 consensus ERK phosphorylation sites (S/T-P)35,36 at amino acid residues 173, 189, 213, and 272 (Figure 2B).

SIGNOR-262916

P24071

P67775

0

dephosphorylation

up-regulates activity

0.323

Furthermore, FcalphaRI activation is induced by protein phosphatase 2A (PP2A) after it dephosphorylates a single serine residue (S263) in the FcalphaRI intracellular tail

SIGNOR-264858

Q5JWF2

P43657

0

binding

up-regulates activity

0.323

LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa.

SIGNOR-278872

P51692

Q15788

0

binding

up-regulates

0.323

Ncoa-1/src-1 is an essential coactivator of stat5 that binds to the fdl motif in the alpha-helical region of the stat5 transactivation domain.

SIGNOR-100261

Q96GD4

Q7Z3K3

0

binding

up-regulates activity

0.323

POGZ is required for the correct activation and dissociation of Aurora B kinase from chromosome arms during M phase. These results reveal POGZ as an essential protein that links HP1alpha dissociation with Aurora B kinase activation during mitosis.

SIGNOR-264497

O60674

Q12913

0

dephosphorylation

down-regulates activity

0.323

These results support PTPRJ preferentially dephosphorylating Y813 and Y868 in JAK2.|We revealed that PTPRJ negatively regulates leptin signaling by dephosphorylating specific tyrosine residues (Y813 and Y868) in JAK2, the simultaneous phosphorylation of which plays a pivotal role in JAK2 activation.

SIGNOR-277094

P10915

P09238

0

cleavage

down-regulates quantity by destabilization

0.323

Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.

SIGNOR-256332

Q9Y6I3

P06493

0

phosphorylation

down-regulates activity

0.323

Phosphorylation of POB1 and Epsin by p34cdc2 kinase. Their phosphorylation sites (Ser411 of POB1 and Ser357 of Epsin) were determined. Phosphorylated Epsin and EpsinS357D formed a complex with α-adaptin less efficiently than wild type Epsin.

SIGNOR-262723

P14210

P03952

0

cleavage

up-regulates activity

0.323

the ability of plasma kallikrein and FXIa to activate pro-HGF in vitro raises the possibility that mediators of inflammation and blood coagulation may also regulate processes that involve the HGF/c-Met pathway, such as tissue repair and angiogenesis.Unlike other known activators, both FXIa and kallikrein processed pro-HGF by cleavage at two sites. Using N-terminal sequencing they were identified as the normal cleavage site Arg(494)-Val(495) and the novel site Arg(424)-His(425) located in the K4 domain of the alpha-chain.

SIGNOR-256513

P08473

P68400

0

phosphorylation

down-regulates

0.323

The cytoplasmic n-terminal domain of nep interacts with the phosphatase and tensin homologue deleted on chromosome 10 (pten) thereby regulating intracellular signaling via akt. Ser 6 is efficiently phosphorylated by protein kinase ck2. The phosphorylation of the cytoplasmic domain of nep inhibits its interaction with pten.

SIGNOR-168673

Q15717

O15111

0

phosphorylation

down-regulates quantity by destabilization

0.323

Furthermore, mutational analysis indicates that IKKα-dependent phosphorylation at Ser-304 is crucial to the binding of HuR to β-TrCP1. Mechanistically, this HuR degradation pathway differs from that reported for heat shock and hypoxia, which underlies the complexity in the regulation of HuR turnover under different stress stimuli.

SIGNOR-276422

P63092

Q96RI0

0

binding

up-regulates activity

0.323

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256772

P42262

P51608

0

transcriptional regulation

down-regulates quantity by repression

0.323

Bicuculline treatment also leads to an increase in the levels of the transcriptional repressor MeCP2, which binds to the GluR2 promoter along with the corepressors HDAC1 and mSin3A.

SIGNOR-264684

P31269

O15550

0

transcriptional regulation

up-regulates quantity by expression

0.323

Evidence for direct involvement of UTX in regulation of HOX gene activity was demonstrated through UTX knockdown experiments in HEK293T cells in which loss of UTX induced transcriptional repression of HOXA and HOXC clusters.

SIGNOR-260025

P41970

P45983

0

phosphorylation

down-regulates activity

0.323

JNK binds to the J box in the middle of the protein, and binding is required for phosphorylation of the adjacent EXport motif. Both the binding and phosphorylation sites (the JEX element) are important for Net export.

SIGNOR-250139

P63092

P43657

0

binding

up-regulates activity

0.323

LPAR1 is reported to associate with Gia,G12/13a,orGqa; LPAR3 with Gia or Gqa; and LPAR6 withGia,G12/13a,orGsa.

SIGNOR-278873

Q12929

P27361

0

phosphorylation

down-regulates activity

0.323

We further show that the actin barbed-end capping activity of Eps8 is inhibited by brain-derived neurotrophic factor (BDNF) treatment through MAPK-dependent phosphorylation of Eps8 residues S624 and T628. Additionally, an Eps8 mutant, impaired in the MAPK target sites (S624A/T628A), displays increased association to actin-rich structures, is resistant to BDNF-mediated release from microfilaments, and inhibits BDNF-induced filopodia. The opposite is observed for a phosphomimetic Eps8 (S624E/T628E) mutant. Thus, collectively, our data identify Eps8 as a critical capping protein in the regulation of axonal filopodia and delineate a molecular pathway by which BDNF, through MAPK-dependent phosphorylation of Eps8, stimulates axonal filopodia formation, a process with crucial impacts on neuronal development and synapse formation.

SIGNOR-263058

P63092

P47900

0

binding

up-regulates activity

0.323

Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0.

SIGNOR-256800

P60953

Q9ULL1

0

guanine nucleotide exchange factor

up-regulates activity

0.323

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-260563

P10415

Q15173

0

dephosphorylation

down-regulates

0.323

Pp2a directly interacts with the bh4 domain of bcl2 as a docking site to potentially bridge pp2a to bcl2's flexible loop domain containing the target serine 70 phosphorylation site.

SIGNOR-181559

P12830

Q12955

0

binding

up-regulates activity

0.323

Ankyrin-G is a molecular partner of E-cadherin in epithelial cells and early embryos. Ankyrin-G also recruits beta-2-spectrin to E-cadherin-beta-catenin complexes, thus providing a direct connection between E-cadherin and the spectrin/actin skeleton.

SIGNOR-266710

P22830

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.322

NFE2L2 is stabilized and translocates to the nucleus, where it dimerizes with sMAF proteins. This complex binds to AREs to mediate the transcription of genes involved in iron metabolism, GSH metabolism, and ROS detoxification.Two critical enzymes in this pathway, ATP binding cassette subfamily B member 6 (ABCB6) and ferrochelatase (FECH), are regulated by the transcription factor NFE2L2 and play significant roles in inhibiting ferroptosis when upregulated.

SIGNOR-279865

Q13263

P62136

0

dephosphorylation

up-regulates activity

0.322

PP1\u03b1 dephosphorylates KAP1 at Ser 824 .

SIGNOR-277075

O43464

P31749

0

phosphorylation

down-regulates

0.322

Akt attenuation of the serine protease activity of htra2/omi through phosphorylation of serine 212

SIGNOR-252500

P18031

P49760

0

phosphorylation

up-regulates activity

0.322

The clk family kinases, clk1 and clk2, phosphorylate and activate the tyrosine phosphatase, ptp-1b.|Phosphorylation of PTP-1B at Ser(50) by CLK1 or CLK2 is responsible for its enzymatic activation.

SIGNOR-70603

Q02952

P06493

0

phosphorylation

up-regulates activity

0.322

Mass spectrometry, molecular, and cellular approaches show that CDK1/Cyclin B1 phosphorylates Gravin on threonine 766 to prime the recruitment of the polo-like kinase Plk1 at defined phases of mitosis.

SIGNOR-271839

P35548

P05771

0

phosphorylation

up-regulates quantity

0.322

PKCbeta increased the level of overexpressed Msx2, but PKC alpha, delta and zeta did not have any significant effects.|Thr135 and Thr141 in Msx2 can be phosphorylated by PKC\u03b2, and Thr135 is important for regulating the protein stability of Msx2 by PKCs.

SIGNOR-278982

P16284

P16591

0

phosphorylation

up-regulates activity

0.322

PECAM-1 Is Phosphorylated by Fer and, To a Lesser Extent, by Fes. These results suggest that Fer not only functions as a tyrosine kinase for PECAM-1 but also that Fer modulates the downstream signaling of PECAM-1 by inducing phosphorylation of SHP-2 and Gab1.

SIGNOR-262866

Q9NRA8

P45983

0

phosphorylation

up-regulates

0.322

Identification of 4e-t phosphorylation sites regulated by jnk. identification of these residues as phosphorylation sites (ser301, ser374, ser513, ser587, ser693, and ser752) was obtained by ms/ms sequencing, these results demonstrate that jnk activity is required to stimulate the assembly of pbs in response to oxidative stress.

SIGNOR-199004

P10915

P09237

0

cleavage

down-regulates quantity by destabilization

0.322

Matrix metalloproteinases cleave at two distinct sites on human cartilage link protein. Sequencing studies of modified link protein components revealed that stromelysins-1 and -2, gelatinases A and B and collagenase cleaved specifically between His16 and Ile17, and matrilysin, stromelysin-2 and gelatinase A cleaved between Leu25 and Leu26. Based on previously determined in situ cleavage sites it is evident that matrix metalloproteinases are not solely responsible for the accumulation of link protein degradation products in adult human cartilage, indicating that additional proteolytic agents are involved in the normal catabolism of human cartilage matrix.

SIGNOR-256329

P22681

P17252

0

phosphorylation

down-regulates quantity

0.322

However, under normal conditions, PKC activation resulting from CD43 engagement was required to activate the MAPK pathway, suggesting that phosphorylation of Cbl on serine residues by PKC and its association with 14-3-3 molecules may play a role in preventing the Cbl inhibitory effect on the Ras-MAPK pathway.

SIGNOR-249056

Q04721

A0PJZ3

0

binding

up-regulates

0.322

We have previously identified two human genes, gxylt1 and gxylt2, encoding glucoside xylosyltransferases responsible for the transfer of xylose to o-linked glucose. The identity of the enzyme further elongating the glycan to generate the final trisaccharide xylose-xylose-glucose, however, remained unknown. Here, we describe that the human gene c3orf21 encodes a udp-xylose:alfa-xyloside alfa1,3-xylosyltransferase, acting on xylose-alfa1,3-glucosebeta1-containing acceptor structures. We have, therefore, renamed it xxylt1 (xyloside xylosyltransferase 1). Xxylt1 cannot act on a synthetic acceptor containing an alfa-linked xylose alone, but requires the presence of the underlying glucose. Activity on notch egf repeats was proven by in vitro xylosylation of a mouse notch1 fragment recombinantly produced in sf9 insect cells, a bacterially expressed egf repeat from mouse notch2 modified in vitro by rumi and gxylt2 and in vivo by co-expression of the enzyme with the notch1 fragment. The enzyme was shown to be a typical type ii membrane-bound glycosyltransferase localized in the endoplasmic reticulum.

SIGNOR-177717

Q14596

P49840

0

phosphorylation

down-regulates activity

0.322

The autophagy receptor NBR1 (neighbor of BRCA1 gene 1) binds UB/ubiquitin and the autophagosome-conjugated MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3) proteins, thereby ensuring ubiquitinated protein degradation|Here we show that NBR1 is a substrate of GSK3. NBR1 phosphorylation by GSK3 at Thr586 prevents the aggregation of ubiquitinated proteins and their selective autophagic degradation.

SIGNOR-261794

Q93034

P17612

0

phosphorylation

up-regulates activity

0.322

Elimination of the S730 but not the T325 PKA phosphorylation site of VACM-1 resulted in a complete inhibition of the VACM-1 activity, thus suggesting a direct effect of PKA on the VACM-1 receptor.

SIGNOR-250352

Q15633

P23443

0

phosphorylation

up-regulates activity

0.322

We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells.

SIGNOR-274068

P27986

Q9H0K1

0

phosphorylation

up-regulates activity

0.322

The Regulatory Subunit of PI3K Is a Direct Catalytic Target of SIK2. These data confirm that p85α is a direct catalytic substrate of SIK2 and that SIK2 S154 phosphorylation significantly increases the activity of the PI3K/AKT pathway in ovarian cancer cells.

SIGNOR-277269

P05787

Q05655

0

phosphorylation

up-regulates

0.322

The present study showed that shear stress, but not stretch, activates PKC delta and phosphorylates K8 Ser-73, which then mediates the disassembly/reorganization of keratin IF in AEC.

SIGNOR-260887

P19404

P12931

0

phosphorylation

up-regulates activity

0.322

Phosphorylation-site analysis selects c-Src targets, including NDUFV2 (NADH dehydrogenase [ubiquinone] flavoprotein 2) at Tyr(193) of respiratory complex I and SDHA (succinate dehydrogenase A) at Tyr(215) of complex II. The phosphorylation of these sites by c-Src is supported by an in vivo assay using cells expressing their phosphorylation-defective mutants.

SIGNOR-276419

P35580

Q14814

0

transcriptional regulation

up-regulates quantity by expression

0.322

Myocyte enhancer factor-2 and serum response factor binding elements regulate fast Myosin heavy chain transcription in vivo. We show that the upstream promoter region of the gene most abundantly expressed in mouse skeletal muscles, IIb MyHC, retains binding activity and transcriptional activation for three positive transcription factors, the serum response factor, Oct-1, and myocyte enhancer factor-2, whereas the other two genes (IIa and IId/x) have nucleotide substitutions in these sites that reduce binding and transcriptional activation

SIGNOR-238766

Q8IXT1

Q9UNE7

0

ubiquitination

down-regulates quantity by destabilization

0.322

HSP70 recruits DDIAS to the CHIP E3 ligase, whereas CHIP promotes the ubiquitination of DDIAS.|However, the findings clearly demonstrated that HSP70 was solely involved in CHIP mediated proteasomal degradation of DDIAS.

SIGNOR-278784

Q14498

P00519

0

phosphorylation

up-regulates activity

0.322

In this paper, we report that RBM39 interacts with the nonreceptor tyrosine kinase c-Abl. Both the Src homology (SH) 2 and SH3 domains of c-Abl interact with RBM39. The major tyrosine phosphorylation sites on RBM39 that are phosphorylated by c-Abl are Y95 and Y99, as demonstrated by liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and mutational analysis. c-Abl was shown boost the transcriptional coactivation activity of RBM39 for ERα and PRβ in a tyrosine kinase-dependent manner.

SIGNOR-262609

Q9UD71

P49674

0

phosphorylation

up-regulates activity

0.322

CKIepsilon phosphorylates and activates DARPP-32, a key molecule in various complex signaling pathways, including dopamine and glutamine signaling, which have both been demonstrated to be main pathways in substance dependence.

SIGNOR-279701

Q05209

P17252

0

phosphorylation

down-regulates

0.322

Ptp-pest is phosphorylated in vitro by both cyclic amp-dependent protein kinase (pka) and protein kinase c (pkc) at two major sites, which we have identified as ser39 and ser435 / phosphorylation of ser39 in vitro decreases the activity of ptp-pest by reducing its affinity for substrate.

SIGNOR-27300

P20338

Q92597

0

binding

up-regulates

0.322

In this report evidence is provided that ndrg1 is a rab4a effector protein that localizes to perinuclear recycling/sorting vesicles in the trans golgi network by binding to phophatidylinositol 4-phosphate and is involved in recycling of e-cadherin. This is the first demonstration providing evidence that ndrg1 is a rab4a effector recruiting to recycling/sorting endosomes.

SIGNOR-157697

Q13362

O96017

0

phosphorylation

up-regulates

0.322

Found that chk2 associated with the b' regulatory subunit of protein phosphatase pp2a. In vitro kinase assays showed that b'gamma3 was a potent chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of pp2a.

SIGNOR-129255

Q9UQ13

P28482

0

phosphorylation

down-regulates quantity by destabilization

0.322

Here, we showed that SHOC2, a RAS activator, is a FBXW7 substrate. Growth stimuli trigger SHOC2 phosphorylation on Thr507 by the mitogen-activated protein kinase (MAPK) signal, which facilitates FBXW7 binding for ubiquitylation and degradation.

SIGNOR-277442

P07203

P42684

0

phosphorylation

up-regulates activity

0.322

GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress.

SIGNOR-104328

Q09472

P20962

0

binding

up-regulates activity

0.322

Macromolecular translocation inhibitor II (MTI-II), which was first identified as an in vitro inhibitor of binding between the highly purified glucocorticoid receptor (GR) and isolated nuclei, is an 11.5-kDa Zn2+-binding protein that is also known as ZnBP or parathymosin. MTI-II Enhances GR-dependent Transcription through Its Acidic Domain. MTI-II Enhances GR-dependent Transcription in Cooperation with SRC-1 and p300 in Vivo. CBP and p300 Coprecipitate with MTI-II in a Glucocorticoid Hormone-dependent Manner. Immunoprecipitation analysis showed that in the presence of glucocorticoid hormone, p300 and CREB-binding protein are coprecipitated with MTI-II. Furthermore, the knockdown of endogenous MTI-II by RNAi reduces the transcriptional activity of GR in cells.

SIGNOR-268461

Q07954

P01009

0

binding

up-regulates

0.322

In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp

SIGNOR-41180

Q8TEA8

O00311

0

phosphorylation

up-regulates activity

0.321

Here we show that DUE-B is de-phosphorylated in M phase and phosphorylated in G1/S phase. Phosphorylated DUE-B forms homodimers, whereas de-phosphorylated DUE-B interacts with the Mcm2–7 complex and aminoacyl-tRNA synthetases. We find that CKII can prime DUE-B for Cdc7 phosphorylation. Confirming the importance of DUE-B phosphorylation in replication initiation, a C-terminal Ser/Thr to Ala mutant blocks Cdc45 and RPA loading on sperm chromatin and inhibits DNA replication. DUE-B C-terminal phosphorylation sites (serine 179, 181, 182, 194, 196, 197, 204, 205, and threonine 187) were mutated to unphosphorylatable alanine (DUE-B(S/T)-A) or phosphomimic aspartic acid (DUE-B(S/T)-D).

SIGNOR-273967

P46937

P49336

0

phosphorylation

up-regulates activity

0.321

CDK8 phosphorylates YAP and promotes its activation. Of interest, mutating four amino acid positions (T119, S128, S289, and S367) to alanines (YAP-4A) completely blocked phosphorylation (Fig. 6J), suggesting that CDK8 phosphorylates these sites in YAP in vitro.

SIGNOR-277651

P28329

P05129

0

phosphorylation

up-regulates

0.321

We show that chat is differentially phosphorylated by protein kinase c (pkc) isoforms on four serines (ser-440, ser-346, ser-347, and ser-476) and one threonine (thr-255). This phosphorylation is hierarchical, with phosphorylation at ser-476 required for phosphorylation at other serines. Phosphorylation at some, but not all, sites regulates basal catalysis and activation.

SIGNOR-129320

Q99259

Q02156

0

phosphorylation

down-regulates activity

0.321

We have identified one specific phosphorylation site, threonine 91 (T91), in hGAD67 that can be phosphorylated by PKA using MALDI-TOF. Site-directed mutation of T91 to alanine abolished PKA-mediated phosphorylation and inhibition of GAD activity.

SIGNOR-249264

Q9BV73

Q9H0K1

0

phosphorylation

down-regulates

0.321

Here, we show that the salt inducible kinase 2 (sik2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, c-nap1, through s2392 phosphorylation

SIGNOR-167488

P04637

Q9BXM7

0

phosphorylation

up-regulates activity

0.321

Our studies thus indicated that mitophagy\npositively regulated hepatic CSCs by suppressing p53, which otherwise would be activated by\nPINK1 to suppress the expression of NANOG and hepatic CSCs.|These results indicated that the phosphorylation of p53 at S392 by\nPINK1 likely took place on mitochondria.

SIGNOR-278418

P49840

P24723

0

phosphorylation

down-regulates

0.321

Furthermore, several pkc isotypes phosphorylate gsk-3 in vitro and in vivo. in the presence of atp, several isoforms (?, ___, _, ?, And of pkc phosphorylated both gsk-3? At ser 21 and gsk-3_ at ser 9

SIGNOR-115730

Q15831

Q05513

0

phosphorylation

up-regulates

0.321

Here, we have identified s307 as a novel phosphorylation site in lkb1 and provide evidence that, in multiple cell types, phosphorylation of this site by protein kinase c ? (pkc-?) Induces nucleocytoplasmic transport of lkb1.

SIGNOR-185640

Q92993

Q16539

0

phosphorylation

up-regulates activity

0.321

We found that phosphorylation of Tip60-T158 was increased by p38\u03b1 isolated from Dox- or \u03b3-radiation-treated cells over that from untreated cells (Figure xref ), indicating that DNA damage induces the protein kinase activity of p38\u03b1 towards Tip60-T158.

SIGNOR-278958

Q13886

P04150

0

transcriptional regulation

up-regulates quantity by expression

0.321

We show that in addition, DEX-bound GR directly promotes the expression of adipogenic TFs, including C/EBPβ, Klf5, Klf9, and C/EBPα

SIGNOR-256119

Q9HC29

P08238

0

binding

up-regulates quantity by stabilization

0.321

Nod2 is constitutively associated with a chaperone protein, Hsp90, which is required for Nod2 stability and protects Nod2 from degradation.

SIGNOR-252415

Q6UUV9

Q13233

0

phosphorylation

up-regulates

0.321

We report on the activation oftorc1through mekk1-mediated phosphorylation.

SIGNOR-180816

Q16143

P34947

0

phosphorylation

down-regulates activity

0.321

GRK5 prefers alpha-synuclein as a substrate. GRK-mediated phosphorylation inhibits synuclein's interaction with both phospholipids and PLD2. Mutation of Ser118 practically abolishes Œ≤-synuclein phosphorylation by both GRK2 and GRK5

SIGNOR-251203

Q9Y281

Q15569

0

phosphorylation

down-regulates activity

0.321

Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin

SIGNOR-246719

Q9Y281

Q96S53

0

phosphorylation

down-regulates activity

0.321

Like TESK1, TESK2 phosphorylated cofilin specifically at Ser-3 and induced formation of actin stress fibers and focal adhesionsExpression of cofilin or S3A-cofilin into HeLa cells induced marked decreases in rhodamine-phalloidin staining due to the actin binding and -depolymerizing activity of cofilin

SIGNOR-246711

P31749

P24666

0

dephosphorylation

down-regulates activity

0.321

Reduction in the levels of both LMW-PTP isoforms in vitro and in vivo increased tyrosine phosphorylation of IR and AktSer473 and increased IRS-1- and IRS-2-associated PI3-K activities in both liver and fat.|Activated PI3-K stimulates Akt (or protein kinase B) that in turn phosphorylates and inactivates glycogen synthase kinase-3

SIGNOR-248455