GleghornLab/Signor_2class · Datasets at Hugging Face

IdA string	IdB string	labels int64	mechanism string	effect string	score float64	sentence string	signor_id string
P30530	Q14511	1	phosphorylation	up-regulates activity	0.2	Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.\|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.	SIGNOR-278905
Q96GD4	O95229	1	phosphorylation	up-regulates activity	0.651	Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores\|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition	SIGNOR-265010
P02461	Q8IYK4	0	glycosylation	up-regulates activity	0.404	Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.	SIGNOR-261158
O60260	Q13002	1	ubiquitination	down-regulates quantity by destabilization	0.2	Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.\|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.	SIGNOR-278541
Q06413	Q9H1R3	0	phosphorylation	up-regulates activity	0.402	Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.	SIGNOR-238118
Q13480	P00533	0	phosphorylation	up-regulates	0.76	Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (egfr)the entire protein was phosphorylated by regfr at eight tyrosine residues (y285, y373, y406, y447, y472, y619, y657, and y689).	SIGNOR-236400
P24385	Q8IYU2	0	ubiquitination	down-regulates quantity by destabilization	0.307	Mechanistically, the tumor-suppressor function of HACE1 is dependent on its E3 ligase activity and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1.	SIGNOR-271405
P14174	P00441	1	relocalization	down-regulates quantity by destabilization	0.307	Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells\|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein	SIGNOR-262797
O95409	Q86T96	0	ubiquitination	down-regulates quantity by destabilization	0.374	Rinescan directly interact with Zic2. the ubiquitination of endogenous Zic2 was enhanced by Myc-Rines in rat neural stem cellline MNS70 cells. Rines-induced degradation of Zic2	SIGNOR-226303
P27361	Q07869	1	phosphorylation	up-regulates activity	0.601	We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.	SIGNOR-249474
Q16584	Q13153	1	phosphorylation	up-regulates activity	0.304	Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.\|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.	SIGNOR-279418
Q5VWQ8	Q969H0	0	ubiquitination	down-regulates quantity by destabilization	0.327	DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1	SIGNOR-254774
P45973	Q5XPI4	0	polyubiquitination	down-regulates quantity by destabilization	0.2	In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.	SIGNOR-272035
Q02156	Q16625	1	phosphorylation	up-regulates	0.2	Thr403, thr404, thr424 and thr438 in the occludin c-terminal domain are the predominant sites of pkc_-dependent phosphorylation . The present study demonstrates that pkc_ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.	SIGNOR-173643
P49841	P53396	1	phosphorylation	up-regulates activity	0.364	Thr 446 and Ser 450, which are phosphorylated by glycogen synthase kinase-3 (GSK-3). Phosphorylation resulted in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal, displaying negative cooperativity, to hyperbolic.	SIGNOR-251219
Q13370	Q14164	0	phosphorylation	up-regulates activity	0.2	While IKK\u03b5 phosphorylates and activates PDE3B to induce catecholamine resistance, TBK1 inhibits AMPK activity to reduce catabolism via this pathway.	SIGNOR-278517
O75385	Q6ZNE5	1	phosphorylation	up-regulates activity	0.651	ULK1 phosphorylates ATG14 at serine 29.	SIGNOR-278433
Q92918	Q9BXL7	1	phosphorylation	up-regulates activity	0.493	HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1. Interestingly, the putative HPK1 phosphorylation sites in CARMA1 are different from known PKC consensus sites. Mutations of residues S549, S551, and S552 in CARMA1 abrogated phosphorylation of a CARMA1-linker construct by HPK1 in vitro.	SIGNOR-276259
Q96J02	P16403	1	polyubiquitination	up-regulates activity	0.2	ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin.	SIGNOR-272926
P17612	Q16891	1	phosphorylation	down-regulates activity	0.2	PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex	SIGNOR-266302
P12931	P09327	1	phosphorylation	up-regulates activity	0.363	These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration.To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton	SIGNOR-247441
P63000	P15882	0	gtpase-activating protein	down-regulates activity	0.666	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-260499
P29474	Q00535	0	phosphorylation	down-regulates	0.371	Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.	SIGNOR-164080
Q01860	P50613	0	phosphorylation	up-regulates quantity by stabilization	0.2	Here, we combined molecular and cellular biology with CRISPR/Cas9-mediated genome engineering to pinpoint the function of serine 12 of OCT4 in ESCs. Using chemical inhibitors and an antibody specific to OCT4 phosphorylated on S12, we identified cyclin-dependent kinase (CDK) 7 as upstream kinase. \|Phosphorylation of OCT4 on S12 has been previously implicated to stabilize OCT4 by binding to PIN1, thereby preventing ubiquitinylation by WWP2.	SIGNOR-264404
Q6IBW4	P53350	0	phosphorylation	up-regulates activity	0.444	Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase.	SIGNOR-278419
P24941	P28324	1	phosphorylation	up-regulates activity	0.363	Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.	SIGNOR-278210
P06493	Q92993	1	phosphorylation	up-regulates	0.478	Moreover, app stabilized tip60 through cdk-dependent phosphorylation	SIGNOR-139653
P67775	Q13188	1	dephosphorylation	down-regulates	0.693	Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.	SIGNOR-201266
Q5TEC6	Q9Y4C1	0	demethylation	up-regulates activity	0.2	Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.	SIGNOR-276843
O94925	P05412	0	transcriptional regulation	up-regulates quantity by expression	0.35	The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression	SIGNOR-268035
P17612	P49748	1	phosphorylation	up-regulates activity	0.2	As shown in Fig. 2C, an in vitro kinase assay carried out using PKA and a GST fusion protein containing the COOH-terminal 258 amino acids showed the protein to be efficiently phosphorylated in a time-dependent manner. \|Furthermore, a phosphorylation-negative mutant (S586A) VLCAD shows reduced electron transfer activity and a strong dominant-negative effect on fatty acid beta-oxidation.	SIGNOR-264422
Q13131	P56524	1	phosphorylation	down-regulates	0.272	We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.	SIGNOR-173689
P36897	Q9HCE7	0	polyubiquitination	down-regulates quantity by destabilization	0.694	Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7.	SIGNOR-272943
Q13564	Q14669	0	ubiquitination	down-regulates quantity by destabilization	0.432	Our data suggest that that TRIP12 promotes degradation of APP-BP1 by catalyzing its ubiquitination, which in turn modulates the neddylation pathway.	SIGNOR-266780
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
O14994	P06493	0	phosphorylation	up-regulates	0.2	A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.	SIGNOR-121398
P36888	P29353	1	phosphorylation	up-regulates activity	0.446	Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313.	SIGNOR-251147
P18846	Q13555	0	phosphorylation	up-regulates activity	0.299	Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.	SIGNOR-250692
O15075	Q6ZN28	1	phosphorylation	up-regulates activity	0.2	Subsequently, MACC1 gets phosphorylated by DCLK1.\|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.	SIGNOR-279031
O94992	Q00987	0	ubiquitination	up-regulates activity	0.465	Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.\|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.	SIGNOR-278701
P31749	P14598	1	phosphorylation	up-regulates	0.559	Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.	SIGNOR-252586
Q8TAS1	P02686	1	phosphorylation	down-regulates	0.2	Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. Mass spectrometry and peptide sequencing allowed us to identify serine 164 of mbp as the unique site phosphorylated by kis. Phosphorylation of synthetic peptides indicated the importance of the proline residue at position +1.	SIGNOR-143485
Q9H4P4	Q8N1B4	1	ubiquitination	down-regulates quantity by destabilization	0.433	RNF41 ubiquitinates and relocates VPS52 away from VPS53, another shared subunit of the GARP and EARP complexes, towards RNF41-positive structures.	SIGNOR-278597
Q13315	Q9Y6D9	1	phosphorylation	up-regulates activity	0.2	ATM mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.\|Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis.	SIGNOR-278467
P01111	Q7Z5G4	0	palmitoylation	up-regulates activity	0.396	Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.	SIGNOR-261354
P17661	P13349	0	transcriptional regulation	up-regulates quantity by expression	0.241	Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression	SIGNOR-241494
Q13131	Q6UUV9	1	phosphorylation	down-regulates	0.285	Here we show that both ampk and calcineurin modulate longevity exclusively through post-translational modification of crtc-1, the sole c. elegans crtc. We demonstrate that crtc-1 is a direct ampk target.	SIGNOR-172136
P04626	P43378	0	dephosphorylation	down-regulates activity	0.304	Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.\|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.	SIGNOR-277170
Q99717	P23771	1	transcriptional regulation	up-regulates quantity	0.31	Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation	SIGNOR-268943
O95835	O14974	1	phosphorylation	up-regulates activity	0.47	LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.\|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.	SIGNOR-278184
O76064	Q14676	0	relocalization	up-regulates	0.757	Rnf8 relocalizes to dna damage sites via a phospho-dependent interaction with mdc1	SIGNOR-179820
O43318	Q9Y4K3	0	ubiquitination	up-regulates activity	0.893	Intriguingly, TGF-beta-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.	SIGNOR-236071
O43683	Q9Y6D9	1	relocalization	up-regulates activity	0.727	Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity	SIGNOR-252017
Q9NZ52	Q9P253	0	monoubiquitination	down-regulates activity	0.506	Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability. By in vitro ubiquitylation assays, we have identified lysine 258 in the GAT domain as a major ubiquitylation site that resides adjacent to the ubiquitin-binding site. Furthermore, the GAT domain ubiquitylated by hVPS18 no longer binds to ubiquitin, indicating that ubiquitylation negatively regulates the ubiquitin-binding ability of the GAT domain. These results suggest that the ubiquitin binding and ubiquitylation of GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of hVPS18.	SIGNOR-271610
P05412	P63244	1	null	up-regulates quantity by expression	0.2	In turn, c-Jun induces expression of RACK1, which is required for JNK activation by PKC, pointing to a c-Jun/RACK1/PKC/JNK feedback loop.	SIGNOR-278066
O14640	P49674	0	phosphorylation	up-regulates activity	0.637	Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development.	SIGNOR-217849
O76064	P0C0S8	1	ubiquitination	up-regulates	0.2	Rnf8 and ubc13 ubiquitylate h2a and h2ax, but other substrates probably exist.	SIGNOR-166174
Q9NZS9	P55061	1	polyubiquitination	down-regulates quantity by destabilization	0.392	BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.	SIGNOR-272778
Q9P2K8	Q9BY44	1	phosphorylation	down-regulates activity	0.484	Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).	SIGNOR-280005
P19367	Q8IYT8	0	phosphorylation	up-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274042
P48050	P00533	0	phosphorylation	up-regulates activity	0.2	These results demonstrate that the EGF receptor tyrosine kinase up-regulates the K(IR) 2.3 channel via phosphorylation of the Y234 residue of the WT protein.	SIGNOR-276322
P46934	Q2KJY2	1	ubiquitination	down-regulates quantity by destabilization	0.316	Nedd4 polyubiquitinates Kif26b and thus targets it for degradation via the ubiquitin-proteasome pathway.	SIGNOR-278767
Q8N8N0	Q7L523	1	polyubiquitination	down-regulates activity	0.74	Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases.	SIGNOR-272222
P33991	O00311	0	phosphorylation	up-regulates	0.958	Activation of the eukaryotic replicative dna helicase, the mcm2-7 complex, requires phosphorylation by cdc7/dbf4 (dbf4-dependent kinase or ddk), which, in turn, depends on prior phosphorylation of mcm2-7 by an unknown kinase (or kinases).we propose that the resulting mec1 modification of mcm4 and mcm6 further activates ddk phosphorylation of mcm2-7 ( fig. 7aii ).	SIGNOR-169453
Q9BXM7	O43464	1	phosphorylation	up-regulates	0.607	Htra2 is phosphorylated on activation of the p38 pathway, occurring in a pink1-dependent mannerwe suggest that pink1-dependent phosphorylation of htra2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.	SIGNOR-158052
Q06418	O43524	1	phosphorylation	down-regulates activity	0.2	However, the present study in tPA and NMDA treated neurons establishes the link between PS mediated activation of Tyro3 and FKHRL1 phosphorylation which inactivates pro apoptotic FKHRL1 and mediates PS 's beneficial effects.\|We also show that inhibition of the extrinsic apoptotic cascade by PS requires Tyro3 mediated phosphorylation of FKHRL1 which in turn inhibits FasL production and FasL dependent caspase-8 activation in the extrinsic pathway.	SIGNOR-279669
P28827	O60716	1	dephosphorylation	down-regulates quantity	0.541	Specifically, RPTP\u03bc dephosphorylated p120 catenin, subsequently leading to a lower level of cytoplasmic protein compared with that observed with the vector control and RPTP\u03bc-CS.	SIGNOR-277042
Q14938	O00712	0	transcriptional regulation	up-regulates quantity	0.42	We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.	SIGNOR-268870
P12931	P48736	0	phosphorylation	up-regulates activity	0.365	PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.	SIGNOR-277225
P49792	Q8TD16	1	relocalization	up-regulates quantity	0.505	We show that the dynein/dynactin adaptor BICD2 is specifically recruited to the NPC in G2phase through a direct interaction with the NPC componentRanBP2.	SIGNOR-259122
P31749	Q12778	1	phosphorylation	down-regulates activity	0.87	Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export.	SIGNOR-236163
P15036	Q15131	0	phosphorylation	down-regulates quantity by destabilization	0.528	Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.	SIGNOR-260914
P01116	P49354	0	null	up-regulates activity	0.382	Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.	SIGNOR-242559
P07948	Q92918	1	phosphorylation	up-regulates activity	0.381	BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.	SIGNOR-251403
Q13554	Q13131	1	phosphorylation	up-regulates	0.2	These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.	SIGNOR-138360
Q9H4A3	Q9BYP7	0	phosphorylation	up-regulates activity	0.282	We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.	SIGNOR-260789
P19419	P28482	0	phosphorylation	up-regulates activity	0.563	We demonstrate that elk-1, a protein closely related to p62tcf in function, is a nuclear target of two members of the map kinase family, erk1 and erk2, erk1 phosphorylates five c-terminal sites in elk-1 (s324,t336, s383, s389 and s422) with varying degrees of efficiency.	SIGNOR-235455
P00519	P29323	1	phosphorylation	down-regulates	0.515	Two-hybrid screens identified regions of abl and arg that bind to the ephb2 and epha4 receptors, suggesting a novel signaling connection involving the two kinase families.The connection between EphB2 and Abl/Arg appears to be reciprocal. Activated EphB2 causes tyrosine phosphorylation of Abl and Arg, and vice versa. Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl.	SIGNOR-109668
Q96JJ3	P63000	1	guanine nucleotide exchange factor	up-regulates activity	0.583	We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth.	SIGNOR-266821
Q9H0X6	P08670	1	ubiquitination	down-regulates quantity by destabilization	0.2	Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells	SIGNOR-269051
Q8NE86	Q13131	0	phosphorylation	up-regulates activity	0.2	Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). \|In vitro kinase assays showed that AMPK immunoprecipitated from cells as well as recombinant AMPK phosphorylated MCU at Ser57	SIGNOR-275547
P15941	P00519	0	phosphorylation	up-regulates quantity by stabilization	0.455	The results demonstrate that ABL1 phosphorylates MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the ABL1 SH2 domain to the pTyr-60 site.	SIGNOR-260830
Q92793	P22087	1	acetylation	down-regulates activity	0.27	Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.\|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. \|Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)	SIGNOR-275897
Q7Z569	Q13107	0	deubiquitination	up-regulates quantity by stabilization	0.268	Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.	SIGNOR-272031
Q06187	P23470	0	dephosphorylation	down-regulates activity	0.262	PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.	SIGNOR-254694
P49841	O75444	1	phosphorylation	down-regulates	0.26	We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.	SIGNOR-159438
Q8IUQ4	Q13535	0	phosphorylation	down-regulates activity	0.2	We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19.	SIGNOR-276167
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
P02686	Q8TAS1	0	phosphorylation	down-regulates	0.2	Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. Mass spectrometry and peptide sequencing allowed us to identify serine 164 of mbp as the unique site phosphorylated by kis. Phosphorylation of synthetic peptides indicated the importance of the proline residue at position +1.	SIGNOR-143485
Q6ZNA4	Q96CW1	1	ubiquitination	up-regulates	0.2	Arkadia ubiquitylated the _?2 Subunit at lys130. In addition, arkadia interacted with the ap2 complex, and modified endocytosis of epidermal growth factor receptor (egfr) induced by egf. Arkadia thus appears to regulate egf signalling by modulating endocytosis of egfr through interaction with ap2 complex.	SIGNOR-168931
P28482	Q92934	1	phosphorylation	down-regulates activity	0.461	The rapid phosphorylation of bad following il-3 connects a proximal survival signal with the bcl-2 family, modulating this checkpoint for apoptosis.phosphorylatedBAD is bound to 14-3-3 within the cytosol, while only nonphosphorylated BAD is heterodimerized with membrane-bound BCL-XL.	SIGNOR-44858
P12931	Q12774	1	phosphorylation	up-regulates activity	0.465	Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.\|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.	SIGNOR-279571
O75385	P08237	1	phosphorylation	down-regulates activity	0.2	Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).	SIGNOR-274035
P10636	Q5TCY1	0	phosphorylation	down-regulates	0.451	Direct tau phosphorylation by ttbk1 at ser198, ser199, ser202 and ser422, which are also phosphorylated in phfs. Ttbk1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that ttbk1 is a neuron-specific dual kinase involved in tau phosphorylation at ad-related sites and is also associated with tau aggregation.	SIGNOR-148970
P49715	P35712	0	transcriptional regulation	up-regulates quantity by expression	0.292	We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST	SIGNOR-255824
O15151	Q96FA3	0	ubiquitination	up-regulates activity	0.434	We found that Peli1 induces Mdmx ubiquitination without promoting its degradation, which leads to the cytoplasmic localization of Mdmx and subsequent activation of p53 function.	SIGNOR-278773
P49736	P68400	0	phosphorylation	up-regulates	0.259	In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2	SIGNOR-144004
P41743	P08151	1	phosphorylation	up-regulates activity	0.402	Although functioning downstream of SMO, aPKC-\u03b9/\u03bb phosphorylates and activates GLI1, resulting in maximal DNA binding and transcriptional activation [ xref ].	SIGNOR-279262
P06241	P22681	1	phosphorylation	up-regulates activity	0.812	Fyn associates with cbl and phosphorylates tyrosine 731 in cbl, a binding site for phosphatidylinositol 3-kinasecbl represents a substrate for src-like kinases that are activated in response to the engagement of cell surface receptors, and that src-like kinases are responsible for the phosphorylation of a tyrosine residue in cbl that may regulate activation of phosphatidylinositol 3-kinase	SIGNOR-63968
P40763	Q14289	0	phosphorylation	up-regulates activity	0.428	These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.\|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).	SIGNOR-279429

P30530

Q14511

1

phosphorylation

up-regulates activity

0.2

Mechanistically, AXL phosphorylates NEDD9, leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1.|These results reveal NEDD9 as a specific AXL substrate.We next validated whether AXL promotes canonical NEDD9 signaling.

SIGNOR-278905

Q96GD4

O95229

1

phosphorylation

up-regulates activity

0.651

Zwint-1 is a novel Aurora B substrate required for the assembly of a dynein-binding platform on kinetochores|During prometaphase, AurB phosphorylation of zwint-1 is required for recruitment of ZW10-, pT89 dynein-, and RZZ-dependent proteins to kinetochores. This is defective after AurB inhibition or after expression of the triple-A zwint-1 mutant. Triple-E mutant zwint-1 mimics phospho–zwint-1 in RZZ recruitment, even after AurB inhibition

SIGNOR-265010

P02461

Q8IYK4

0

glycosylation

up-regulates activity

0.404

Recombinant GLT25D1 and GLT25D2 enzymes showed a strong galactosyltransferase activity toward various types of collagen and toward the serum mannose-binding lectin MBL, which contains a collagen domain. Amino acid analysis of the products of GLT25D1 and GLT25D2 reactions confirmed the transfer of galactose to hydroxylysine residues.

SIGNOR-261158

O60260

Q13002

1

ubiquitination

down-regulates quantity by destabilization

0.2

Parkin interacts with and ubiquitinates the GluK2 KAR subunit and regulates GluK2 levels and KAR currents.|The loss of parkin function increases surface and total GluK2 levels, and consistently increases KAR currents.

SIGNOR-278541

Q06413

Q9H1R3

0

phosphorylation

up-regulates activity

0.402

Here, we show that phosphorylation of MEF2C on T(80) by skeletal myosin light chain kinase (skMLCK) enhances skeletal and not cardiac myogenesis.

SIGNOR-238118

Q13480

P00533

0

phosphorylation

up-regulates

0.76

Gab-1 is a multisubstrate docking protein downstream in the signaling pathways of different receptor tyrosine kinases, including the epidermal growth factor receptor (egfr)the entire protein was phosphorylated by regfr at eight tyrosine residues (y285, y373, y406, y447, y472, y619, y657, and y689).

SIGNOR-236400

P24385

Q8IYU2

0

ubiquitination

down-regulates quantity by destabilization

0.307

Mechanistically, the tumor-suppressor function of HACE1 is dependent on its E3 ligase activity and HACE1 controls adhesion-dependent growth and cell cycle progression during cell stress through degradation of cyclin D1.

SIGNOR-271405

P14174

P00441

1

relocalization

down-regulates quantity by destabilization

0.307

Here, we show that MIF inhibits mutant SOD1 nuclear clearance when overexpressed in motor neuron-like NSC-34 cells|SOD1WT is evenly distributed between the cytoplasm and the nucleus while mutant SOD1G93A shows predominantly cytoplasmic distribution (Fig. 1a, b). Expression of MIF in cells expressing SOD1WT had no effect on the distribution of the SOD1WT–EGFP protein. However, expression of MIF together with the mutant SOD1G93A–EGFP, inhibited the nuclear clearance of misfolded SOD1 resulting in a more wild-type-like distribution of the mutant SOD1 protein

SIGNOR-262797

O95409

Q86T96

0

ubiquitination

down-regulates quantity by destabilization

0.374

Rinescan directly interact with Zic2. the ubiquitination of endogenous Zic2 was enhanced by Myc-Rines in rat neural stem cellline MNS70 cells. Rines-induced degradation of Zic2

SIGNOR-226303

P27361

Q07869

1

phosphorylation

up-regulates activity

0.601

We now demonstrate that amino acids 1-92 of hPPARalpha contain an activation function (AF)-1-like domain, which is further activated by insulin through a pathway involving the mitogen-activated protein kinases p42 and p44. Further analysis of the amino-terminal region of PPARalpha revealed that the insulin-induced trans-activation occurs through the phosphorylation of two mitogen-activated protein kinase sites at positions 12 and 21, both of which are conserved across evolution.

SIGNOR-249474

Q16584

Q13153

1

phosphorylation

up-regulates activity

0.304

Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3.|MLK3 was able to directly phosphorylate PAK1 on two Serine residues of which Ser204 is critical for MLK3-induced PAK1 activation and downstream functions.

SIGNOR-279418

Q5VWQ8

Q969H0

0

ubiquitination

down-regulates quantity by destabilization

0.327

DAB2IP protein levels can be negatively regulated by the activity of the E3-ubiquitin ligases Fbw7, Skp2, and Smurf1

SIGNOR-254774

P45973

Q5XPI4

0

polyubiquitination

down-regulates quantity by destabilization

0.2

In the present study, we report that HP1α and β undergo proteasomal degradation in lamin A/C knock-down cells and show by ectopic expression, RNAi and binding studies that the RING finger ubiquitin ligase RNF123 is directly involved in HP1 degradation.

SIGNOR-272035

Q02156

Q16625

1

phosphorylation

up-regulates

0.2

Thr403, thr404, thr424 and thr438 in the occludin c-terminal domain are the predominant sites of pkc_-dependent phosphorylation . The present study demonstrates that pkc_ phosphorylates occludin on specific threonine residues and promotes assembly of epithelial tight junctions.

SIGNOR-173643

P49841

P53396

1

phosphorylation

up-regulates activity

0.364

Thr 446 and Ser 450, which are phosphorylated by glycogen synthase kinase-3 (GSK-3). Phosphorylation resulted in a 6-fold increase in V(max) and the conversion of citrate dependence from sigmoidal, displaying negative cooperativity, to hyperbolic.

SIGNOR-251219

Q13370

Q14164

0

phosphorylation

up-regulates activity

0.2

While IKK\u03b5 phosphorylates and activates PDE3B to induce catecholamine resistance, TBK1 inhibits AMPK activity to reduce catabolism via this pathway.

SIGNOR-278517

O75385

Q6ZNE5

1

phosphorylation

up-regulates activity

0.651

ULK1 phosphorylates ATG14 at serine 29.

SIGNOR-278433

Q92918

Q9BXL7

1

phosphorylation

up-regulates activity

0.493

HPK1 interacts with CARMA1 in a TCR stimulation-dependent manner and phosphorylates the linker region of CARMA1. Interestingly, the putative HPK1 phosphorylation sites in CARMA1 are different from known PKC consensus sites. Mutations of residues S549, S551, and S552 in CARMA1 abrogated phosphorylation of a CARMA1-linker construct by HPK1 in vitro.

SIGNOR-276259

Q96J02

P16403

1

polyubiquitination

up-regulates activity

0.2

ITCH interacts with and ubiquitinates linker histone H1.2 at K46. ITCH biochemically competes with RNF168 and RNF8 to polyubiquitinate histone H1.2. The results indicated that ITCH-mediated K46-Ubn is essential for the binding of histone H1.2 to chromatin.

SIGNOR-272926

P17612

Q16891

1

phosphorylation

down-regulates activity

0.2

PKA directly phosphorylated the Ser528 residue of MIC60. Phosphorylation of MIC60 Interrupts Parkin Recruitment and Formation of the MICOS Complex

SIGNOR-266302

P12931

P09327

1

phosphorylation

up-regulates activity

0.363

These data suggest that phosphorylation of villin by c-src is involved in the actin cytoskeleton remodeling necessary for cell migration.To further investigate the role of tyrosine phosphorylated villin in cell migration, we used phosphorylation site mutants (tyrosine to phenylalanine or tyrosine to glutamic acid) in HeLa cells. We determined that tyrosine phosphorylation at residues 60, 81, and 256 of human villin played an essential role in cell migration as well as in the reorganization of the actin cytoskeleton

SIGNOR-247441

P63000

P15882

0

gtpase-activating protein

down-regulates activity

0.666

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-260499

P29474

Q00535

0

phosphorylation

down-regulates

0.371

Together, our data suggest that cdk5 can phosphorylate enos at the ser-113 site and down-regulate enos-derived no levels.

SIGNOR-164080

Q01860

P50613

0

phosphorylation

up-regulates quantity by stabilization

0.2

Here, we combined molecular and cellular biology with CRISPR/Cas9-mediated genome engineering to pinpoint the function of serine 12 of OCT4 in ESCs. Using chemical inhibitors and an antibody specific to OCT4 phosphorylated on S12, we identified cyclin-dependent kinase (CDK) 7 as upstream kinase. |Phosphorylation of OCT4 on S12 has been previously implicated to stabilize OCT4 by binding to PIN1, thereby preventing ubiquitinylation by WWP2.

SIGNOR-264404

Q6IBW4

P53350

0

phosphorylation

up-regulates activity

0.444

Plk1 phosphorylation of CAP-H2 at Ser288 is required for the accumulation of CAP-H2 and accurate chromosomal condensation during prophase.

SIGNOR-278419

P24941

P28324

1

phosphorylation

up-regulates activity

0.363

Phosphorylation of ELK4 at Thr194 and Ser387 by CDK2 is required for EGF-induced cell transformation.

SIGNOR-278210

P06493

Q92993

1

phosphorylation

up-regulates

0.478

Moreover, app stabilized tip60 through cdk-dependent phosphorylation

SIGNOR-139653

P67775

Q13188

1

dephosphorylation

down-regulates

0.693

Rassf1a apparently protects mst1/2 against inactivation by pp2a, the phosphatases that dephosphorylate the stimulatory thr-183 and thr-180 of mst1 andmst2, respectively.

SIGNOR-201266

Q5TEC6

Q9Y4C1

0

demethylation

up-regulates activity

0.2

Using a biochemical assay coupled with chromatography, we have purified a JmjC domain-containing protein, JHDM2A, which specifically demethylates mono- and dimethyl-H3K9.

SIGNOR-276843

O94925

P05412

0

transcriptional regulation

up-regulates quantity by expression

0.35

The transcription factor c-Jun can directly bind to the GLS gene promoter and enhance expression

SIGNOR-268035

P17612

P49748

1

phosphorylation

up-regulates activity

0.2

As shown in Fig. 2C, an in vitro kinase assay carried out using PKA and a GST fusion protein containing the COOH-terminal 258 amino acids showed the protein to be efficiently phosphorylated in a time-dependent manner. |Furthermore, a phosphorylation-negative mutant (S586A) VLCAD shows reduced electron transfer activity and a strong dominant-negative effect on fatty acid beta-oxidation.

SIGNOR-264422

Q13131

P56524

1

phosphorylation

down-regulates

0.272

We show here that in liver, class iia hdacs (hdac4, 5, and 7) are phosphorylated and excluded from the nucleus by ampk family kinases.

SIGNOR-173689

P36897

Q9HCE7

0

polyubiquitination

down-regulates quantity by destabilization

0.694

Here we show that Smurf1, an E3 ubiquitin ligase for bone morphogenetic protein-specific Smads, also interacts with Smad7 and induces Smad7 ubiquitination and translocation into the cytoplasm. In addition, Smurf1 associates with TbetaR-I via Smad7, with subsequent enhancement of turnover of TbetaR-I and Smad7.

SIGNOR-272943

Q13564

Q14669

0

ubiquitination

down-regulates quantity by destabilization

0.432

Our data suggest that that TRIP12 promotes degradation of APP-BP1 by catalyzing its ubiquitination, which in turn modulates the neddylation pathway.

SIGNOR-266780

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

O14994

P06493

0

phosphorylation

up-regulates

0.2

A rare, missense polymorphism, s470n, was identified in the synapsin iii gene and appeared more frequently in individuals with schizophrenia than in controls. Ser470, was determined to be a substrate for mitogen-activated protein kinase, a downstream effector of neurotrophin action.

SIGNOR-121398

P36888

P29353

1

phosphorylation

up-regulates activity

0.446

Intracellular FLT3 signaling involves tyrosine phosphorylation of several cytoplasmic proteins including SHC. We have found that upon FLT3 activation SHC phosphorylation occurs at tyrosine 239/240 and 313.

SIGNOR-251147

P18846

Q13555

0

phosphorylation

up-regulates activity

0.299

Phosphopeptide mapping analysis and Western blotting studies demonstrated that in vitro, CaMK II phosphorylates only Ser63 (corresponding to Ser133 of CREB), which is essential for the activation, and not Ser72 (corresponding to Ser142 of CREB), which is a negative regulation site.

SIGNOR-250692

O15075

Q6ZN28

1

phosphorylation

up-regulates activity

0.2

Subsequently, MACC1 gets phosphorylated by DCLK1.|This might be attributed to the higher activation of MACC1 by DCLK1 in the MACC1-positive cell lines SW620/Control and SW480/MACC1 used in this study.

SIGNOR-279031

O94992

Q00987

0

ubiquitination

up-regulates activity

0.465

Here we report that human double minute-2 protein (HDM2), a p53-specific E3 ubiquitin ligase, specifically ubiquitinates HEXIM1 through the lysine residues located within the basic region of HEXIM1.|However, the HDM2-induced HEXIM1 ubiquitination does not lead to proteasome-mediated protein degradation.

SIGNOR-278701

P31749

P14598

1

phosphorylation

up-regulates

0.559

Akt phosphorylates p47phox and mediates respiratory burst activity in human neutrophils. A direct interaction between p47(phox) and akt was shown. Active recombinant akt phosphorylated recombinant p47(phox) in vitro. Mutation analysis indicated that 2 aa residues, ser(304) and ser(328), were phosphorylated by akt. Inhibition of akt activity also inhibited fmlp-stimulated neutrophil chemotaxis.

SIGNOR-252586

Q8TAS1

P02686

1

phosphorylation

down-regulates

0.2

Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. Mass spectrometry and peptide sequencing allowed us to identify serine 164 of mbp as the unique site phosphorylated by kis. Phosphorylation of synthetic peptides indicated the importance of the proline residue at position +1.

SIGNOR-143485

Q9H4P4

Q8N1B4

1

ubiquitination

down-regulates quantity by destabilization

0.433

RNF41 ubiquitinates and relocates VPS52 away from VPS53, another shared subunit of the GARP and EARP complexes, towards RNF41-positive structures.

SIGNOR-278597

Q13315

Q9Y6D9

1

phosphorylation

up-regulates activity

0.2

ATM mediated Mad1 Serine 214 phosphorylation regulates Mad1 dimerization and the spindle assembly checkpoint.|Together, these findings reveal an important role of ATM-mediated Mad1 Serine 214 phosphorylation in mitosis.

SIGNOR-278467

P01111

Q7Z5G4

0

palmitoylation

up-regulates activity

0.396

Covalent lipid modifications mediate the membrane attachment and biological activity of Ras proteins. All Ras isoforms are farnesylated and carboxyl-methylated at the terminal cysteine; H-Ras and N-Ras are further modified by palmitoylation. Here we report that H- and N-Ras are palmitoylated by a human protein palmitoyltransferase encoded by the ZDHHC9 and GCP16 genes. DHHC9 is an integral membrane protein that contains a DHHC cysteine-rich domain. GCP16 encodes a Golgi-localized membrane protein.

SIGNOR-261354

P17661

P13349

0

transcriptional regulation

up-regulates quantity by expression

0.241

Desmin, the muscle specific intermediate filament (IF) protein, is expressed at low levels in myoblasts and at the onset of differentiation its expression increases several fold. In an effort to explore the mechanism involved in the tissue-specific and developmentally regulated expression of desmin, we have isolated the mouse desmin gene.Co-transfection of myoD, myogenin, MRF4 and Myf5, with the desmin-CAT construct into 10T-1/2 cells demonstrated that all these factors could transactivate desmin gene expression

SIGNOR-241494

Q13131

Q6UUV9

1

phosphorylation

down-regulates

0.285

Here we show that both ampk and calcineurin modulate longevity exclusively through post-translational modification of crtc-1, the sole c. elegans crtc. We demonstrate that crtc-1 is a direct ampk target.

SIGNOR-172136

P04626

P43378

0

dephosphorylation

down-regulates activity

0.304

Conversely, increasing expression of PTPN9 wild type (WT) inhibits tyrosyl phosphorylation of ErbB2 and EGFR.|Protein-tyrosine phosphatase PTPN9 negatively regulates ErbB2 and epidermal growth factor receptor signaling in breast cancer cells.

SIGNOR-277170

Q99717

P23771

1

transcriptional regulation

up-regulates quantity

0.31

Chromatin immunoprecipitation (ChIP) revealed a subset of the BIG (BMP4 induced genes) signature, including Satb2, Smad6, Hand1, Gadd45γ and Gata3, that was bound by Smad1/5 in the developing mandible, revealing direct Smad-mediated regulation

SIGNOR-268943

O95835

O14974

1

phosphorylation

up-regulates activity

0.47

LATS1 directly and preferentially phosphorylated serine 445 (S445) of MYPT1.|This suggests that LATS1 promotes MYPT1 to antagonize PLK1 activity.

SIGNOR-278184

O76064

Q14676

0

relocalization

up-regulates

0.757

Rnf8 relocalizes to dna damage sites via a phospho-dependent interaction with mdc1

SIGNOR-179820

O43318

Q9Y4K3

0

ubiquitination

up-regulates activity

0.893

Intriguingly, TGF-beta-induced TRAF6-mediated Lys 63-linked polyubiquitylation of TAK1 Lys 34 correlates with TAK1 activation. Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6.

SIGNOR-236071

O43683

Q9Y6D9

1

relocalization

up-regulates activity

0.727

Spindle checkpoint protein Bub1 is required for kinetochore localization of Mad1, Mad2, Bub3, and CENP-E, independently of its kinase activity

SIGNOR-252017

Q9NZ52

Q9P253

0

monoubiquitination

down-regulates activity

0.506

Monoubiquitylation of GGA3 by hVPS18 regulates its ubiquitin-binding ability. By in vitro ubiquitylation assays, we have identified lysine 258 in the GAT domain as a major ubiquitylation site that resides adjacent to the ubiquitin-binding site. Furthermore, the GAT domain ubiquitylated by hVPS18 no longer binds to ubiquitin, indicating that ubiquitylation negatively regulates the ubiquitin-binding ability of the GAT domain. These results suggest that the ubiquitin binding and ubiquitylation of GGA3-GAT domain are mutually inseparable through a ubiquitin ligase activity of hVPS18.

SIGNOR-271610

P05412

P63244

1

null

up-regulates quantity by expression

0.2

In turn, c-Jun induces expression of RACK1, which is required for JNK activation by PKC, pointing to a c-Jun/RACK1/PKC/JNK feedback loop.

SIGNOR-278066

O14640

P49674

0

phosphorylation

up-regulates activity

0.637

Phenotypic analysis of mutant mDvl-1 indicates that phosphorylation of these sites stimulates the Dvl-activated beta-catenin-dependent Wnt signaling pathway in both cell culture and in Xenopus development.

SIGNOR-217849

O76064

P0C0S8

1

ubiquitination

up-regulates

0.2

Rnf8 and ubc13 ubiquitylate h2a and h2ax, but other substrates probably exist.

SIGNOR-166174

Q9NZS9

P55061

1

polyubiquitination

down-regulates quantity by destabilization

0.392

BAR overexpression promotes BI-1 ubiquitination and proteasomal degradation.We show here that bifunctional apoptosis regulator (BAR) functions as an ER-associated RING-type E3 ligase, interacts with BI-1, and promotes proteasomal degradation of BI-1.

SIGNOR-272778

Q9P2K8

Q9BY44

1

phosphorylation

down-regulates activity

0.484

Activated GCN2 phosphorylates and inhibits eukaryotic translation initiation factor 2A (eIF2\u03b1), leading to a transient reduction in protein synthesis, while enhancing the translation of ATF4 ( xref ), a transcription factor that activates stress-induced gene expression ( xref \u2013 xref ).

SIGNOR-280005

P19367

Q8IYT8

0

phosphorylation

up-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274042

P48050

P00533

0

phosphorylation

up-regulates activity

0.2

These results demonstrate that the EGF receptor tyrosine kinase up-regulates the K(IR) 2.3 channel via phosphorylation of the Y234 residue of the WT protein.

SIGNOR-276322

P46934

Q2KJY2

1

ubiquitination

down-regulates quantity by destabilization

0.316

Nedd4 polyubiquitinates Kif26b and thus targets it for degradation via the ubiquitin-proteasome pathway.

SIGNOR-278767

Q8N8N0

Q7L523

1

polyubiquitination

down-regulates activity

0.74

Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. The mutation of RagA ubiquitination sites abolishes this effect of RNF152 and enhances the RagA-mediated activation of mTORC1. Ubiquitination by RNF152 generates an anchor on RagA to recruit its inhibitor GATOR1, a GAP complex for Rag GTPases.

SIGNOR-272222

P33991

O00311

0

phosphorylation

up-regulates

0.958

Activation of the eukaryotic replicative dna helicase, the mcm2-7 complex, requires phosphorylation by cdc7/dbf4 (dbf4-dependent kinase or ddk), which, in turn, depends on prior phosphorylation of mcm2-7 by an unknown kinase (or kinases).we propose that the resulting mec1 modification of mcm4 and mcm6 further activates ddk phosphorylation of mcm2-7 ( fig. 7aii ).

SIGNOR-169453

Q9BXM7

O43464

1

phosphorylation

up-regulates

0.607

Htra2 is phosphorylated on activation of the p38 pathway, occurring in a pink1-dependent mannerwe suggest that pink1-dependent phosphorylation of htra2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.

SIGNOR-158052

Q06418

O43524

1

phosphorylation

down-regulates activity

0.2

However, the present study in tPA and NMDA treated neurons establishes the link between PS mediated activation of Tyro3 and FKHRL1 phosphorylation which inactivates pro apoptotic FKHRL1 and mediates PS 's beneficial effects.|We also show that inhibition of the extrinsic apoptotic cascade by PS requires Tyro3 mediated phosphorylation of FKHRL1 which in turn inhibits FasL production and FasL dependent caspase-8 activation in the extrinsic pathway.

SIGNOR-279669

P28827

O60716

1

dephosphorylation

down-regulates quantity

0.541

Specifically, RPTP\u03bc dephosphorylated p120 catenin, subsequently leading to a lower level of cytoplasmic protein compared with that observed with the vector control and RPTP\u03bc-CS.

SIGNOR-277042

Q14938

O00712

0

transcriptional regulation

up-regulates quantity

0.42

We report that, in the absence of Nfia or Nfib, there is a marked reduction in the spinal cord expression of NFIX, and that NFIB can transcriptionally activate Nfix expression in vitro. These data demonstrate that NFIX is part of the downstream transcriptional program through which NFIA and NFIB coordinate gliogenesis within the spinal cord.

SIGNOR-268870

P12931

P48736

0

phosphorylation

up-regulates activity

0.365

PI3Kγ mediated phosphorylation of Src enhances Src activity protein kinase activity of PI3K phosphorylates serine residue 70 on Src to enhance its activity and induce EGFR transactivation following βAR stimulation.

SIGNOR-277225

P49792

Q8TD16

1

relocalization

up-regulates quantity

0.505

We show that the dynein/dynactin adaptor BICD2 is specifically recruited to the NPC in G2phase through a direct interaction with the NPC componentRanBP2.

SIGNOR-259122

P31749

Q12778

1

phosphorylation

down-regulates activity

0.87

Here we show that the activation of phosphatidylinositol 3 (PI3) kinase by extracellular growth factors induces phosphorylation, nuclear export, and transcriptional inactivation of FKHR1, a member of the FKHR subclass of the forkhead family of transcription factors. Protein kinase B (PKB)/Akt, a key mediator of PI3 kinase signal transduction, phosphorylated recombinant FKHR1 in vitro at threonine-24 and serine-253. Mutants FKHR1(T24A), FKHR1(S253A), and FKHR1(T24A/S253A) were resistant to both PKB/Akt-mediated phosphorylation and PI3 kinase-stimulated nuclear export.

SIGNOR-236163

P15036

Q15131

0

phosphorylation

down-regulates quantity by destabilization

0.528

Altogether, these results suggest that CDK10/cyclin M directly controls ETS2 degradation through the phosphorylation of these two serines.

SIGNOR-260914

P01116

P49354

0

null

up-regulates activity

0.382

Major investments have been made to target Ras through indirect routes. Inhibition of farnesyl transferase to block Ras maturation has failed in large clinical trials.

SIGNOR-242559

P07948

Q92918

1

phosphorylation

up-regulates activity

0.381

BCR ligation induced rapid tyrosine-phosphorylation of HPK1 mainly by Syk and Lyn, resulting in its association with BASH and catalytic activation. Tyr-379 within HPK1 is essential for binding to BASH and thus strongly suggest that the DDDYDDV sequence containing the phosphorylated Tyr-379 is the binding site for the BASH SH2 domain.

SIGNOR-251403

Q13554

Q13131

1

phosphorylation

up-regulates

0.2

These data indicate that the camkks function in intact cells as ampkks, predicting wider roles for these kinases in regulating ampk activity in vivo.

SIGNOR-138360

Q9H4A3

Q9BYP7

0

phosphorylation

up-regulates activity

0.282

We found that wild-type WNK2 (Figure 8A) or WNK3 (Figure 8B) phosphorylated kinase-inactive WNK1 (1–667, D368A) at Ser382 in vitro.

SIGNOR-260789

P19419

P28482

0

phosphorylation

up-regulates activity

0.563

We demonstrate that elk-1, a protein closely related to p62tcf in function, is a nuclear target of two members of the map kinase family, erk1 and erk2, erk1 phosphorylates five c-terminal sites in elk-1 (s324,t336, s383, s389 and s422) with varying degrees of efficiency.

SIGNOR-235455

P00519

P29323

1

phosphorylation

down-regulates

0.515

Two-hybrid screens identified regions of abl and arg that bind to the ephb2 and epha4 receptors, suggesting a novel signaling connection involving the two kinase families.The connection between EphB2 and Abl/Arg appears to be reciprocal. Activated EphB2 causes tyrosine phosphorylation of Abl and Arg, and vice versa. Interestingly, treatment of COS cells and B35 neuronal-like cells with ephrin-B1 to activate endogenous EphB2 decreased the kinase activity of endogenous Abl.

SIGNOR-109668

Q96JJ3

P63000

1

guanine nucleotide exchange factor

up-regulates activity

0.583

We found in this study that AUTS2 is involved in Rac1 activation via P-Rex1 and the Elmo2/Dock180 complex, but not STEF or Tiam1, for the lamellipodia formation in N1E-115 cells. However, the enhancement of neurite elongation in primary neurons by AUTS2 expression is specifically mediated by the Elmo2/Dock180 complex. These results suggested that several Rac-GEFs differentially or cooperatively participate in Rac1 activation to promote neuronal migration and neurite outgrowth.

SIGNOR-266821

Q9H0X6

P08670

1

ubiquitination

down-regulates quantity by destabilization

0.2

Here, we show that RING finger protein 208 (RNF208) decreases the stability of soluble Vimentin protein through a polyubiquitin-mediated proteasomal degradation pathway, thereby suppressing metastasis of TNBC cells

SIGNOR-269051

Q8NE86

Q13131

0

phosphorylation

up-regulates activity

0.2

Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). |In vitro kinase assays showed that AMPK immunoprecipitated from cells as well as recombinant AMPK phosphorylated MCU at Ser57

SIGNOR-275547

P15941

P00519

0

phosphorylation

up-regulates quantity by stabilization

0.455

The results demonstrate that ABL1 phosphorylates MUC1 on Tyr-60 and forms a complex with MUC1 by binding of the ABL1 SH2 domain to the pTyr-60 site.

SIGNOR-260830

Q92793

P22087

1

acetylation

down-regulates activity

0.27

Here, we show that FBL is acetylated at several lysine residues by the acetyltransferase CBP and deacetylated by SIRT7.|hyperacetylation impairs the interaction of FBL with histone H2A and chromatin, thereby compromising H2AQ104 methylation (H2AQ104me) and rDNA transcription. SIRT7-dependent deacetylation of FBL ensures H2AQ104me and high levels of rRNA synthesis during interphase. |Global acetylome studies have shown that FBL is acetylated at four conserved lysine residues (K102, K121, K205, and K206)

SIGNOR-275897

Q7Z569

Q13107

0

deubiquitination

up-regulates quantity by stabilization

0.268

Here we report on a novel interaction between the E3 ligase BRAP (also referred to as IMP), a negative regulator of the MAPK scaffold protein KSR, and two closely related deubiquitylases, USP15 and USP4. USP15 as well as USP4 oppose the autoubiquitylation of BRAP, whereas BRAP promotes the ubiquitylation of USP15.

SIGNOR-272031

Q06187

P23470

0

dephosphorylation

down-regulates activity

0.262

PTPRG activation by the P1-WD peptide affected the tyrosine phosphorylation of several signaling molecules. Data analysis identified 31 molecules whose phosphorylation was modified in a statistically significant manner (Table I). inhibition of ABL1, BMX, BTK, DAB1, ITGB1, JAK2, KDR, KIT, LIMK1, MET, PDGFRB, SHC1, and VCL correlates with tyrosine dephosphorylation. In contrast, SRC inhibition correlates with hyperphosphorylation of the inhibitory Tyr530 residue and with dephosphorylation of the activatory Tyr419. Moreover, CDK2 and CTTN inhibition correlates with a hyperphosphorylation of the inhibitory Tyr15 and Tyr470, respectively. In contrast, a subgroup of 13 proteins, including BLNK, DOK2, ERBB2, GRIN2B, INSR, PDGFRA, PRKCD, PXN, STAT1, STAT2, STAT3, STAT5A, and ZAP70, appears to be activated by PTPRG activity.

SIGNOR-254694

P49841

O75444

1

phosphorylation

down-regulates

0.26

We showed that c-maf and mafb, like mafa, are indeed phosphorylated by gsk-3/ we demonstrated that phosphorylation by gsk-3 is conserved among the large maf proteins. It couples ubiquitination/degradation and transcriptional activation and modulates maf biological activity.

SIGNOR-159438

Q8IUQ4

Q13535

0

phosphorylation

down-regulates activity

0.2

We have also demonstrated that DNA damage triggers disruption of the HIPK2-Siah-1 complex, resulting in HIPK2 stabilization and activation. Disruption of the HIPK2-Siah-1 complex is mediated by the ATM/ATR pathway and involves ATM/ATR-dependent phosphorylation of Siah-1 at Ser 19.

SIGNOR-276167

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

P02686

Q8TAS1

0

phosphorylation

down-regulates

0.2

Phosphorylation decreased the ability of mbp to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the mbp-actin complex or on the ability of ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the mbp-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. Mass spectrometry and peptide sequencing allowed us to identify serine 164 of mbp as the unique site phosphorylated by kis. Phosphorylation of synthetic peptides indicated the importance of the proline residue at position +1.

SIGNOR-143485

Q6ZNA4

Q96CW1

1

ubiquitination

up-regulates

0.2

Arkadia ubiquitylated the _?2 Subunit at lys130. In addition, arkadia interacted with the ap2 complex, and modified endocytosis of epidermal growth factor receptor (egfr) induced by egf. Arkadia thus appears to regulate egf signalling by modulating endocytosis of egfr through interaction with ap2 complex.

SIGNOR-168931

P28482

Q92934

1

phosphorylation

down-regulates activity

0.461

The rapid phosphorylation of bad following il-3 connects a proximal survival signal with the bcl-2 family, modulating this checkpoint for apoptosis.phosphorylatedBAD is bound to 14-3-3 within the cytosol, while only nonphosphorylated BAD is heterodimerized with membrane-bound BCL-XL.

SIGNOR-44858

P12931

Q12774

1

phosphorylation

up-regulates activity

0.465

Arhgef5 was tyrosine-phosphorylated by Src and bound to Src to positively regulate its activity.|Using an inducible system for Src activation, we found that Src induced podosome formation depends upon the Src SH3 domain, and identified Arhgef5 as a Src SH3 binding protein.

SIGNOR-279571

O75385

P08237

1

phosphorylation

down-regulates activity

0.2

Here, we demonstrate that, during deprivation of amino acid and growth factors, ULK1/2 directly phosphorylate key glycolytic enzymes including hexokinase (HK), phosphofructokinase 1 (PFK1), enolase 1 (ENO1), and the gluconeogenic enzyme fructose-1,6-bisphosphatase (FBP1).Phosphorylation of these enzymes leads to enhanced HK activity to sustain glucose uptake but reduced activity of FBP1 to block the gluconeogenic route and reduced activity of PFK1 and ENO1 to moderate drop of glucose-6-phosphate and to repartition more carbon flux to pentose phosphate pathway (PPP), maintaining cellular energy and redox homeostasis at cellular and organismal levels.Similar results were also obtained using ULK2 as the kinase (data not shown).

SIGNOR-274035

P10636

Q5TCY1

0

phosphorylation

down-regulates

0.451

Direct tau phosphorylation by ttbk1 at ser198, ser199, ser202 and ser422, which are also phosphorylated in phfs. Ttbk1 also induces tau aggregation in human neuronal cells in a dose-dependent manner. We conclude that ttbk1 is a neuron-specific dual kinase involved in tau phosphorylation at ad-related sites and is also associated with tau aggregation.

SIGNOR-148970

P49715

P35712

0

transcriptional regulation

up-regulates quantity by expression

0.292

We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST

SIGNOR-255824

O15151

Q96FA3

0

ubiquitination

up-regulates activity

0.434

We found that Peli1 induces Mdmx ubiquitination without promoting its degradation, which leads to the cytoplasmic localization of Mdmx and subsequent activation of p53 function.

SIGNOR-278773

P49736

P68400

0

phosphorylation

up-regulates

0.259

In this work, by in vitro kinase reactions and mass spectrometry analysis of the products, we have mapped phosphorylation sites in the n terminus of mcm2 by cdc7, cdk2, cdk1, and ck2

SIGNOR-144004

P41743

P08151

1

phosphorylation

up-regulates activity

0.402

Although functioning downstream of SMO, aPKC-\u03b9/\u03bb phosphorylates and activates GLI1, resulting in maximal DNA binding and transcriptional activation [ xref ].

SIGNOR-279262

P06241

P22681

1

phosphorylation

up-regulates activity

0.812

Fyn associates with cbl and phosphorylates tyrosine 731 in cbl, a binding site for phosphatidylinositol 3-kinasecbl represents a substrate for src-like kinases that are activated in response to the engagement of cell surface receptors, and that src-like kinases are responsible for the phosphorylation of a tyrosine residue in cbl that may regulate activation of phosphatidylinositol 3-kinase

SIGNOR-63968

P40763

Q14289

0

phosphorylation

up-regulates activity

0.428

These results imply that following EGF stimulation, PYK2 enhances a STAT3-dependent IL8 expression, thus creating a positive feedback loop between ErbB receptors, PYK2, and IL8.|These results suggest that PYK2-induced STAT3 phosphorylation is crucial for IL8 secretion, while IL8 is crucial for EGF-induced MMP9 transcription (Figure xref ) and for SKBR3 invasion (Figure xref ).

SIGNOR-279429