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
P13807	P49840	phosphorylation	down-regulates	0.411	Glycogen synthase kinase-3 (gsk-3) phosphorylates four serine residues in the cooh terminus of glycogen synthase. Phosphorylation of one of these residues, ser640 (site 3a), causes strong inactivation of glycogen synthase	SIGNOR-118927
P15311	Q5S007	phosphorylation	up-regulates activity	0.411	LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.	SIGNOR-279202
P33981	P24941	phosphorylation	up-regulates quantity by stabilization	0.411	Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).	SIGNOR-279398
P11021	Q15011	relocalization	up-regulates quantity by stabilization	0.411	A key inhibitor of the turnover and Nt-arginylation of BiP was HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation.	SIGNOR-261346
P07900	Q9P278	binding	down-regulates activity	0.411	FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.	SIGNOR-261414
Q92823	P54762	phosphorylation	up-regulates activity	0.411	EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.	SIGNOR-262862
Q02880	Q13315	phosphorylation	down-regulates quantity by destabilization	0.411	Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.	SIGNOR-277510
P54253	P31749	phosphorylation	up-regulates quantity by stabilization	0.411	Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.	SIGNOR-252561
Q16621	P45983	phosphorylation	down-regulates quantity by destabilization	0.411	Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.	SIGNOR-275552
Q02577	Q8TAP4	binding	up-regulates activity	0.411	Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma.	SIGNOR-254827
O14757	P06493	phosphorylation	up-regulates	0.411	Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency	SIGNOR-175071
P63096	Q13304	binding	up-regulates activity	0.411	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 ≥ -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 ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-256692
Q13571	Q96J02	polyubiquitination	down-regulates quantity by destabilization	0.411	Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.	SIGNOR-272721
P30307	P45983	phosphorylation	down-regulates	0.411	Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.	SIGNOR-164089
Q9H2B2	P45983	phosphorylation	up-regulates activity	0.411	JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.	SIGNOR-273673
P06239	P06241	phosphorylation	down-regulates activity	0.411	In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.\|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.	SIGNOR-279986
Q08211	Q9BRS8	binding	up-regulates activity	0.41	La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.	SIGNOR-273500
P10275	Q6ZRS2	binding	up-regulates activity	0.41	The SNF2-related CBP activator protein (SRCAP) serves as a coactivator for several nuclear receptors including the androgen receptor (AR). SRCAP is an ATPase that is the core subunit of a large multiprotein complex and was shown to incorporate the histone variant H2A.Z into nucleosomes. In this report, we demonstrate that SRCAP is expressed in the epithelium of normal prostate and in prostate carcinoma cells, and is associated with AR in the nucleus	SIGNOR-255221
Q15109	P58753	binding	up-regulates activity	0.41	These results indicate that TIRAP functions as an essential adaptor protein for RAGE, binding to ligand-activated phosphorylated RAGE and transducing a signal from it.	SIGNOR-280459
P60953	Q5TG30	gtpase-activating protein	down-regulates activity	0.41	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-260497
O60674	P00519	phosphorylation	up-regulates activity	0.41	Jak2 peptide substrate studies indicated that the Bcr-Abl and Abl tyrosine kinases specifically phosphorylated Y1007 of Jak2 but only poorly phosphorylated Y1008. Phosphorylation of Y1007 of Jak2 is known to be critical for its tyrosine kinase activation.	SIGNOR-245365
O43255	Q92630	phosphorylation	up-regulates	0.41	In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis.	SIGNOR-198729
P63000	Q15669	relocalization	down-regulates activity	0.41	Therefore, RhoH functions as a Rac1 antagonist by inhibiting Rac1 translocation to the cell plasma membrane in the regulation of cell migration and F-actin assembly of HPCs	SIGNOR-259085
Q9P1W9	P42229	transcriptional regulation	up-regulates quantity by expression	0.41	The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.	SIGNOR-249622
P36956	P17676	transcriptional regulation	up-regulates quantity	0.41	These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis	SIGNOR-251645
Q9UHD2	P35813	dephosphorylation	down-regulates activity	0.41	Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.\|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).\|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.	SIGNOR-276966
Q14191	P00519	phosphorylation	up-regulates	0.41	We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.	SIGNOR-86497
P24385	Q9Y463	phosphorylation	down-regulates	0.41	Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells	SIGNOR-150126
P04150	O15516	transcriptional regulation	down-regulates quantity by repression	0.41	We recently reported that the basic helix-loop- helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the 'lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids.	SIGNOR-253699
Q9P0L2	Q15831	phosphorylation	up-regulates	0.41	Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold	SIGNOR-122545
P15172	P40424	binding	up-regulates activity	0.41	These domains are necessary for the stable binding of myod to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein pbx, which appears to be constitutively bound at this site	SIGNOR-124834
Q92879	P31749	phosphorylation	up-regulates activity	0.41	In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.	SIGNOR-280173
P06733	P12931	phosphorylation	up-regulates	0.41	The present finding suggested that the tyrosine residue at position 44 in chicken alpha-enolase is the phosphorylation site by the tyrosine kinase. Our data suggest that eno1 was upregulated by caga protein through activating the src and mek/erk signal pathways	SIGNOR-205092
Q05469	Q13131	phosphorylation	down-regulates	0.41	Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.	SIGNOR-58255
O75030	Q15418	phosphorylation	down-regulates	0.41	The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert.	SIGNOR-174760
Q15013	P53350	phosphorylation	down-regulates activity	0.41	Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.	SIGNOR-265970
Q96Q89	P06493	phosphorylation	up-regulates activity	0.41	Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.	SIGNOR-262695
Q13418	Q13153	phosphorylation	up-regulates	0.41	We found that pak1 phosphorylates ilk at threonine-173 and serine-246 in vitro and in vivo. together, these results suggest that ilk is a pak1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin.	SIGNOR-154303
Q12955	Q6ZMI3	relocalization	up-regulates quantity	0.41	Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.	SIGNOR-266725
Q92519	Q9HCE7	ubiquitination	down-regulates quantity by destabilization	0.41	In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.	SIGNOR-275432
Q969H0	P31749	phosphorylation	up-regulates activity	0.41	A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.	SIGNOR-276328
O15350	Q9H4B4	phosphorylation	down-regulates activity	0.41	In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.\|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.	SIGNOR-279647
Q14524	Q92913	binding	down-regulates activity	0.41	Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.	SIGNOR-253415
P02452	Q8NBJ5	glycosylation	up-regulates activity	0.41	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-261152
Q03060	P27361	phosphorylation	down-regulates quantity by destabilization	0.41	The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.	SIGNOR-275978
Q6R327	P49841	phosphorylation	down-regulates quantity by destabilization	0.409	We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.	SIGNOR-276898
O00592	P19544	transcriptional regulation	up-regulates quantity by expression	0.409	Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.	SIGNOR-252300
Q86UR1	Q5TCZ1	binding	up-regulates activity	0.409	Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner\|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein\|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation	SIGNOR-264708
Q02078	Q13469	binding	up-regulates	0.409	Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.	SIGNOR-117586
Q13285	P10275	binding	up-regulates	0.409	Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.	SIGNOR-109996
P20340	O43896	relocalization	up-regulates quantity	0.409	Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.	SIGNOR-266877
P04637	Q13464	phosphorylation	up-regulates quantity	0.409	Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.	SIGNOR-280108
P48735	Q9NXA8	catalytic activity	up-regulates activity	0.409	Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.	SIGNOR-261212
P50222	P15863	binding	up-regulates activity	0.409	We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.	SIGNOR-222232
P35222	P36888	phosphorylation	up-regulates activity	0.409	Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.	SIGNOR-260124
O43609	Q06124	dephosphorylation	down-regulates	0.409	These results identify sprouty proteins as in vivo targets of corkscrew/shp-2 tyrosine phosphatases and show how corkscrew/shp-2 proteins can promote rtk signaling by inactivating a feedback inhibitor.	SIGNOR-144547
P19174	P63211	binding	up-regulates	0.409	Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.	SIGNOR-199144
Q9H2G9	Q9NTX7	ubiquitination	down-regulates quantity by destabilization	0.409	Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.	SIGNOR-263340
Q7L591	P07948	phosphorylation	up-regulates activity	0.409	An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.	SIGNOR-268447
Q9NS23	P11802	phosphorylation	down-regulates	0.409	This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.	SIGNOR-159849
Q01484	O00533	relocalization	up-regulates quantity	0.409	Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.	SIGNOR-266722
P00533	P42685	phosphorylation	down-regulates activity	0.409	Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.\|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants.	SIGNOR-279177
Q12888	Q96GD4	phosphorylation	up-regulates activity	0.409	Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.	SIGNOR-264411
Q14457	P19484	transcriptional regulation	up-regulates quantity by expression	0.409	As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;	SIGNOR-276558
P60709	Q9Y4I1	binding	up-regulates activity	0.409	Myosin Va regulates exocytosis of large dense-core vesicles (LDCVs). interestingly, inhibition of myosin Va potentiates LDCV exocytosis to the same extent as F-actin depolymerization does, suggesting that myosin Va cooperates with the actin cytoskeleton to impede or control LDCV exocytosis	SIGNOR-269280
Q9Y365	P68400	phosphorylation	down-regulates	0.409	Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity	SIGNOR-155740
P26678	Q13976	phosphorylation	up-regulates activity	0.409	Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.	SIGNOR-279269
Q68CZ2	P12931	phosphorylation	up-regulates	0.408	Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate	SIGNOR-187843
Q9P2Y5	P42345	phosphorylation	up-regulates activity	0.408	MTOR phosphorylates UVRAG at serine 550 and serine 571	SIGNOR-276919
Q13469	P48454	dephosphorylation	up-regulates activity	0.408	NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity	SIGNOR-248512
Q13507	Q13976	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142961
Q13507-3	Q13976	phosphorylation	down-regulates	0.408	The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.	SIGNOR-142957
Q86UR1	P12931	phosphorylation	up-regulates	0.408	Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.	SIGNOR-168545
P07101	Q00535	phosphorylation	up-regulates activity	0.408	In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.\|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.	SIGNOR-279022
Q13541	Q9H0H3	binding	down-regulates quantity by destabilization	0.408	We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.	SIGNOR-272049
Q14344	Q96RI0	binding	up-regulates	0.408	Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13)	SIGNOR-196015
P17275	Q96J02	polyubiquitination	down-regulates quantity by destabilization	0.408	Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.	SIGNOR-272619
Q01130	Q13627	phosphorylation	down-regulates activity	0.408	Dyrk1A inhibits SC35\u2032s activity to promote tau exon 10 inclusion.\|Dyrk1A interacts with and phosphorylates SC35 and inhibits its activity to promote tau exon 10 inclusion.	SIGNOR-278307
Q01453	P16144	binding	up-regulates activity	0.408	PMP22 is in a complex with α6β4 integrin and laminin. PMP22 and β4 integrin are in a complex in a variety of cell types. The interaction with the integrins provides PMP22 with the ability to modulate the cell–ECM communications, as well as intracellular events. Signaling between the ECM and the intracellular compartment is essential for SC myelination, as well as cellular differentiation and motility, in general. The identification of PMP22 as a binding partner for an integrin signaling complex provides a major step toward understanding the role of this disease-linked molecule in the nervous system and in non-neural cell types.	SIGNOR-251896
P50148	Q9NPG1	binding	up-regulates	0.408	Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.	SIGNOR-122895
Q14524	Q13554	phosphorylation	up-regulates activity	0.408	Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).\|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. \| Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5	SIGNOR-275773
Q9H492	Q8IXH6	binding	up-regulates	0.408	Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1	SIGNOR-182614
Q9BV73	Q96CN5	binding	up-regulates activity	0.408	Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin	SIGNOR-273703
P30291	P68400	phosphorylation	down-regulates quantity by destabilization	0.408	In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.	SIGNOR-276038
P00441	Q16236	transcriptional regulation	up-regulates quantity by expression	0.408	BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2	SIGNOR-254653
Q8TDD2	Q16539	phosphorylation	up-regulates activity	0.408	We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes	SIGNOR-255791
O14490	Q00535	phosphorylation	down-regulates quantity by destabilization	0.408	Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.	SIGNOR-279153
P20226	Q12947	binding	up-regulates activity	0.408	The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.	SIGNOR-220373
Q92911	Q06710	transcriptional regulation	up-regulates quantity by expression	0.408	Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.	SIGNOR-251990
Q16539	P35813	dephosphorylation	down-regulates activity	0.408	Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay	SIGNOR-59618
P30679	P41231	binding	up-regulates activity	0.408	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 ≥ -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 ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257031
P36888	P43405	phosphorylation	up-regulates activity	0.407	Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).\|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.	SIGNOR-278431
P15927	Q9NUX5	binding	down-regulates activity	0.407	The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA	SIGNOR-263324
Q15717	P06493	phosphorylation	down-regulates activity	0.407	Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.\|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.	SIGNOR-279014
P29597	P08575	dephosphorylation	down-regulates activity	0.407	CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling\|these results show that CD45 dephosphorylates functionally important tyrosine residues. It should be noted that, as with our phosphatase assays in vitro, Tyr 1022 and Tyr 1023 of JAK1, Tyr 1007 and Tyr 1008 of JAK2, and Tyr 1054 and Tyr 1055 of Tyk2 are indeed hyperphosphorylated in cd45-deficient cells	SIGNOR-248357
Q92558	P12931	phosphorylation	up-regulates	0.407	The wave/scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the arp2/3 complex in response to extracellular cues.Src-dependent phosphorylation of scar1 promotes its association with the arp2/3 complex	SIGNOR-142724
O95837	Q9UNW8	binding	up-regulates activity	0.407	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 ≥ -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 ≥ -1.0 for defining true couplings. \| The score associated to this interaction has a LogRAi ≥ -1.0.	SIGNOR-257396
P63092	Q13255	binding	up-regulates activity	0.407	MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.	SIGNOR-264077
P42680	Q08881	phosphorylation	up-regulates	0.407	Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated	SIGNOR-98090
P52732	Q8TDX7	phosphorylation	up-regulates activity	0.407	NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.	SIGNOR-273890

P13807

P49840

0

phosphorylation

down-regulates

0.411

Glycogen synthase kinase-3 (gsk-3) phosphorylates four serine residues in the cooh terminus of glycogen synthase. Phosphorylation of one of these residues, ser640 (site 3a), causes strong inactivation of glycogen synthase

SIGNOR-118927

P15311

Q5S007

0

phosphorylation

up-regulates activity

0.411

LRRK2 also phosphorylated ezrin and radixin, which are related to moesin, at the residue equivalent to Thr558, as well as a peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558.

SIGNOR-279202

P33981

P24941

0

phosphorylation

up-regulates quantity by stabilization

0.411

Cdk2 phosphorylates Mps1 at T468, attenuating the function of a degradation signal found in amino acids 420\u2013507 (encoded by exons 12 and 13) and allowing the accumulation of a centrosomal pool of Mps1 that represents no more than 10% of total cellular Mps1 ( xref ).

SIGNOR-279398

P11021

Q15011

0

relocalization

up-regulates quantity by stabilization

0.411

A key inhibitor of the turnover and Nt-arginylation of BiP was HERP (homocysteine-responsive ER protein), a 43-kDa ER membrane-integrated protein that is an essential component of ER-associated protein degradation.

SIGNOR-261346

P07900

Q9P278

0

binding

down-regulates activity

0.411

FNIP1 and FNIP2 facilitate FLCN binding to Hsp90 chaperone. Our results suggest that FNIP1 is a potent inhibitor of Hsp90 ATPase activity, as 200 nM of FNIP1 inhibits Hsp90 ATPase activity by 50-fold. FNIP2 also has shown inhibitory activity towards Hsp90; however, it required 1.6 μM of FNIP2 to inhibit the ATPase activity by eightfold. Although we use the term ‘inhibition' here, FNIPs seem only to be slowing the chaperone cycle.

SIGNOR-261414

Q92823

P54762

0

phosphorylation

up-regulates activity

0.411

EphB receptors were found to induce phosphorylation of NrCAM on the tyrosine residue within the FIGQY ankyrin binding motif, inhibiting ankyrin recruitment. Furthermore, NrCAM phospho-FIGQY levels in the SC were decreased in EphB1/3 and EphB1/2/3 null mice and increased in mutant mice overexpressing constitutively active EphB2 kinase.

SIGNOR-262862

Q02880

Q13315

0

phosphorylation

down-regulates quantity by destabilization

0.411

Specifically, DNA damage signal, triggered by teniposide (VM-26) treatment, activates ATM, cooperating with CK1 to phosphorylate TOP2β on Ser1134 and Ser1130, respectively, in a canonical degron motif to facilitate β-TrCP binding and subsequent degradation.ATM binds with and phosphorylates TOP2β at Ser1134 to promote its degradation by VM-26.

SIGNOR-277510

P54253

P31749

0

phosphorylation

up-regulates quantity by stabilization

0.411

Interaction of Ataxin-1 and 14-3-3 Requires Akt Phosphorylation at S776. 14-3-3 protein, a multifunctional regulatory molecule, mediates the neurotoxicity of ataxin-1 by binding to and stabilizing ataxin-1, thereby slowing its normal degradation.

SIGNOR-252561

Q16621

P45983

0

phosphorylation

down-regulates quantity by destabilization

0.411

Through use of different approaches including nano-scale proteomics, we show that activated-JNK, or Phospho-JNK (P-JNK), physically interacts with p45/NF-E2 and phosphorylates its Ser157 residue. This reaction leads to the poly-ubiquitination of p45/NF-E2 at one or more of six Lys residues, one of which being also a sumoylation site, and its degradation through the proteasome pathway.

SIGNOR-275552

Q02577

Q8TAP4

0

binding

up-regulates activity

0.411

Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma.

SIGNOR-254827

O14757

P06493

0

phosphorylation

up-regulates

0.411

Chk1 itself is also subject to cdk-mediated phosphorylation at serines 286 and 301 (s286 and 301). We show that chk1 s301 phosphorylation increases as cells progress through s and g2 and that both cdk1 and cdk2 are likely to contribute to this modification in vivo. We also find that substitution of s286 and s301 with non-phosphorylatable alanine residues strongly attenuates dna damage-induced chk1 activation and g2 checkpoint proficiency

SIGNOR-175071

P63096

Q13304

0

binding

up-regulates activity

0.411

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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-256692

Q13571

Q96J02

0

polyubiquitination

down-regulates quantity by destabilization

0.411

Here, we found that the level of LAPTM5 protein is regulated negatively by the degradation through ubiquitination by ITCH, an E3 ubiquitin ligase. ITCH directly binds to the PPxY motif of LAPTM5 via its WW domains and promotes ubiquitination through a HECT-type ligase domain.

SIGNOR-272721

P30307

P45983

0

phosphorylation

down-regulates

0.411

Here we show that jnk directly phosphorylates cdc25c at serine 168 during g(2) phase of the cell cycle. Cdc25c phosphorylation by jnk negatively regulates its phosphatase activity and thereby cdk1 activation, enabling a timely control of mitosis onset.

SIGNOR-164089

Q9H2B2

P45983

0

phosphorylation

up-regulates activity

0.411

JNK phosphorylates Syt 4 at Ser135 in vitro and in vivo.

SIGNOR-273673

P06239

P06241

0

phosphorylation

down-regulates activity

0.411

In nonactivated T cells, CCR7 triggering induced a Fyn dependent phosphorylation of the inhibitory Tyr505 of Lck.|Inhibiting Fyn in these nonactivated T cells prevented the negative regulation of Lck and facilitated high CCR7 driven T cell chemotaxis.

SIGNOR-279986

Q08211

Q9BRS8

0

binding

up-regulates activity

0.41

La ribonucleoprotein domain family member 6 (LARP6) is the protein that binds 5' SL with high affinity and specificity and coordinates their translation. Here we show that RNA helicase A (RHA) is tethered to the 5' SL of collagen mRNAs by interaction with the C-terminal domain of LARP6.

SIGNOR-273500

P10275

Q6ZRS2

0

binding

up-regulates activity

0.41

The SNF2-related CBP activator protein (SRCAP) serves as a coactivator for several nuclear receptors including the androgen receptor (AR). SRCAP is an ATPase that is the core subunit of a large multiprotein complex and was shown to incorporate the histone variant H2A.Z into nucleosomes. In this report, we demonstrate that SRCAP is expressed in the epithelium of normal prostate and in prostate carcinoma cells, and is associated with AR in the nucleus

SIGNOR-255221

Q15109

P58753

0

binding

up-regulates activity

0.41

These results indicate that TIRAP functions as an essential adaptor protein for RAGE, binding to ligand-activated phosphorylated RAGE and transducing a signal from it.

SIGNOR-280459

P60953

Q5TG30

0

gtpase-activating protein

down-regulates activity

0.41

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-260497

O60674

P00519

0

phosphorylation

up-regulates activity

0.41

Jak2 peptide substrate studies indicated that the Bcr-Abl and Abl tyrosine kinases specifically phosphorylated Y1007 of Jak2 but only poorly phosphorylated Y1008. Phosphorylation of Y1007 of Jak2 is known to be critical for its tyrosine kinase activation.

SIGNOR-245365

O43255

Q92630

0

phosphorylation

up-regulates

0.41

In the present study, we identify the serine/threonine kinase dyrk2 as siah2 interaction partner that phosphorylates siah2 at five residues (ser16, thr26, ser28, ser68, and thr119). accordingly, phosphorylated siah2 is more active than the wild-type e3 ligase and shows an increased ability to trigger the hif-1?-Mediated transcriptional response and angiogenesis.

SIGNOR-198729

P63000

Q15669

0

relocalization

down-regulates activity

0.41

Therefore, RhoH functions as a Rac1 antagonist by inhibiting Rac1 translocation to the cell plasma membrane in the regulation of cell migration and F-actin assembly of HPCs

SIGNOR-259085

Q9P1W9

P42229

0

transcriptional regulation

up-regulates quantity by expression

0.41

The results of 2 microarray experiments demonstrated that the aberrant activation of STAT proteins by Flt3-ITDs resulted in the up-regulation of several STAT5-responsive genes, such as Pim-1, Pim-2, and members of the SOCS (suppressor of cytokine signaling) protein family. These results are particularly interesting because recent data point to an important role of Pim kinases in the antiapoptosis of hematopoietic cells.

SIGNOR-249622

P36956

P17676

0

transcriptional regulation

up-regulates quantity

0.41

These results show that GSK3β is involved in regulating phosphorylation and activation of C/EBPβ and that this transcription factor is required to transactivate srebf1a expression, leading to the early steps of adipogenesis

SIGNOR-251645

Q9UHD2

P35813

0

dephosphorylation

down-regulates activity

0.41

Furthermore, PPM1A, but not PPM1B, serves as an efficient phosphatase to dephosphorylate Ser 172 residue of both TBK1 and IKKepsilon kinases, which is critical for their kinase activities.|In a similar in vitro phosphatase assay, incubation of PPM1A also eliminated TBK1 and IKKepsilon phosphorylation at Ser 172 residue, evidenced by phospho-S172 immunoblotting (XREF_FIG, F and G).|These observations suggest that PPM1A may block kinase activities of TBK1 and IKKepsilon.

SIGNOR-276966

Q14191

P00519

0

phosphorylation

up-regulates

0.41

We thus hypothesized that wrn may interact with the abl tyrosine kinase in the dna damage response. Here, we provide evidence for a functional and physical interaction between wrn and c-abl, including wrn relocalization in response to dna damage, suggesting that this protein-protein interaction participates in a shared pathway of genome surveillance.

SIGNOR-86497

P24385

Q9Y463

0

phosphorylation

down-regulates

0.41

Further, we found that not only gsk-3beta but also dyrk1b modulates cyclin d1 subcellular localization by the phosphorylation of thr(288). These results suggest that dif-3 induces degradation of cyclin d1 through the gsk-3beta- and dyrk1b-mediated threonine phosphorylation in hela cells

SIGNOR-150126

P04150

O15516

0

transcriptional regulation

down-regulates quantity by repression

0.41

We recently reported that the basic helix-loop- helix transcription factor Clock, which is a histone acetyltransferase and a central component of the self-oscillating transcription factor loop that generates circadian rhythms, represses GR transcriptional activity by acetylating lysine residues within the 'lysine cluster' located in the hinge region of the receptor. This Clock-mediated repression of GR transcriptional activity oscillates in inverse phase to the HPA axis, acting as a target tissue counter-regulatory mechanism to the diurnally fluctuating circulating glucocorticoids.

SIGNOR-253699

Q9P0L2

Q15831

0

phosphorylation

up-regulates

0.41

Lkb1 is a master kinase that activates 13 kinases of the ampk subfamily, including mark/par-1we recently demonstrated that the lkb1 tumour suppressor kinase, in complex with the pseudokinase strad and the scaffolding protein mo25, phosphorylates and activates amp-activated protein kinase (ampk). A total of 12 human kinases (nuak1, nuak2, brsk1, brsk2, qik, qsk, sik, mark1, mark2, mark3, mark4 and melk) are related to ampk. Here we demonstrate that lkb1 can phosphorylate the t-loop of all the members of this subfamily, apart from melk, increasing their activity >50-fold

SIGNOR-122545

P15172

P40424

0

binding

up-regulates activity

0.41

These domains are necessary for the stable binding of myod to the myogenin promoter through an interaction with an adjacent protein complex containing the homeodomain protein pbx, which appears to be constitutively bound at this site

SIGNOR-124834

Q92879

P31749

0

phosphorylation

up-regulates activity

0.41

In normal myoblasts, Akt kinase phosphorylates CUGBP1 at Ser28 and increases interactions of CUGBP1 with cyclin D1 mRNA.

SIGNOR-280173

P06733

P12931

0

phosphorylation

up-regulates

0.41

The present finding suggested that the tyrosine residue at position 44 in chicken alpha-enolase is the phosphorylation site by the tyrosine kinase. Our data suggest that eno1 was upregulated by caga protein through activating the src and mek/erk signal pathways

SIGNOR-205092

Q05469

Q13131

0

phosphorylation

down-regulates

0.41

Phosphorylation of bovine hormone-sensitive lipase by the amp-activated protein kinase.

SIGNOR-58255

O75030

Q15418

0

phosphorylation

down-regulates

0.41

The current study reveals that c-kit signaling triggers two phosphorylation events on mi, which up-regulate transactivation potential yet simultaneously target mi for ubiquitin-dependent proteolysis. The specific activation/degradation signals derive from mapk/erk targeting of serine 73, whereas serine 409 serves as a substrate for p90 rsk-1. An unphosphorylatable double mutant at these two residues is at once profoundly stable and transcriptionally inert.

SIGNOR-174760

Q15013

P53350

0

phosphorylation

down-regulates activity

0.41

Purified Plk1 bound to p31comet and phosphorylated it, resulting in the suppression of its activity (with TRIP13) to disassemble checkpoint complexes. We conclude that Plk1 phosphorylates p31 on S102 and on five additional sites. The phosphorylation of the additional sites was possibly not detectable in HeLa cell extracts due to the opposing action of protein phosphatases.

SIGNOR-265970

Q96Q89

P06493

0

phosphorylation

up-regulates activity

0.41

Here we report the identification of a novel KRP, termed KRMP1, which undergoes in vivo phosphorylation. The carboxyl-terminal globular tail domain is strongly phosphorylated by mitotic kinase activities almost attributed to cdc2 kinase, which is responsible for phosphorylation on residue Thr-1604 of KRMP1.

SIGNOR-262695

Q13418

Q13153

0

phosphorylation

up-regulates

0.41

We found that pak1 phosphorylates ilk at threonine-173 and serine-246 in vitro and in vivo. together, these results suggest that ilk is a pak1 substrate, undergoes phosphorylation-dependent shuttling between the cell nucleus and cytoplasm, and interacts with gene-regulatory chromatin.

SIGNOR-154303

Q12955

Q6ZMI3

0

relocalization

up-regulates quantity

0.41

Ankyrin-G is recruited to the nodes of Ranvier by gliomedin, which is produced by Schwann cells and accumulates in the perinodal extracellular matrix. As a ligand for neurofascin-186, gliomedin causes the nodal clustering of this cell adhesion molecule, which in turn recruits to the nodal plasma membrane an ankyrin-G protein network consisting of voltage-gated sodium or potassium channels (KCNQ2/3) and β4-spectrin.

SIGNOR-266725

Q92519

Q9HCE7

0

ubiquitination

down-regulates quantity by destabilization

0.41

In this study, we found that TRIB2 was up-regulated and exhibited high stability in liver cancer cells compared with other cells. We performed a structure-function analysis of TRIB2 and identified a domain (amino acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1 and was critical for protein stability. Deletion of this domain extended TRIB2 half-life time accompanied with a more significant malignant property compared with wild type TRIB2.

SIGNOR-275432

Q969H0

P31749

0

phosphorylation

up-regulates activity

0.41

A reciprocal immunoprecipiation with anti-phospho-Akt substrate antibody followed by immunoblotting with anti-FLAG antibodies confirmed these findings (Fig. 1C). We concluded that Fbw7 is phosphorylated at S227 in vivo. Phosphorylation of Fbw7 is required for its biological activity.

SIGNOR-276328

O15350

Q9H4B4

0

phosphorylation

down-regulates activity

0.41

In this study, we found that Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.|Plk3 inhibits pro-apoptotic activity of p73 through physical interaction and phosphorylation.

SIGNOR-279647

Q14524

Q92913

0

binding

down-regulates activity

0.41

Sodium channel fast inactivation is modulated by alpha subunit interaction with a family of cytoplasmic proteins termed fibroblast growth factor homologous factors (FHFs). In this paper, we report that all A-type FHFs exert rapid onset long-term inactivation on Nav1.6 and other sodium channels.

SIGNOR-253415

P02452

Q8NBJ5

0

glycosylation

up-regulates activity

0.41

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-261152

Q03060

P27361

0

phosphorylation

down-regulates quantity by destabilization

0.41

The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway.

SIGNOR-275978

Q6R327

P49841

0

phosphorylation

down-regulates quantity by destabilization

0.409

We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability.

SIGNOR-276898

O00592

P19544

0

transcriptional regulation

up-regulates quantity by expression

0.409

Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself.

SIGNOR-252300

Q86UR1

Q5TCZ1

0

binding

up-regulates activity

0.409

Tks4 and Tks5 bind NoxA1 through their SH3 domains in a Rac-independent manner|NoxO1 is required for full Nox1 and Nox3 oxidase activity at least partially because of its role in the plasma membrane recruitment of the NoxA1 activator protein|Tks4 and Tks5 support Nox1- and Nox3-dependent ROS generation

SIGNOR-264708

Q02078

Q13469

0

binding

up-regulates

0.409

Upon dephosphorylation by calcineurin, nfatc2, also referred to as nfatp/nfat1, translocates to the nucleus where it directly associates with mef2a and -d. Nfatc2 stimulates mef2-dependent transcription by facilitating recruitment of the p300 coactivator to mef2-response elements.

SIGNOR-117586

Q13285

P10275

0

binding

up-regulates

0.409

Ar suppresses transcription of the lhbeta subunit by interacting with steroidogenic factor-1.

SIGNOR-109996

P20340

O43896

0

relocalization

up-regulates quantity

0.409

Here, we identify Bicaudal-D-related protein 1 (BICDR-1) as an effector of the small GTPase Rab6 and key component of the molecular machinery that controls secretory vesicle transport in developing neurons. BICDR-1 interacts with kinesin motor Kif1C, the dynein/dynactin retrograde motor complex, regulates the pericentrosomal localization of Rab6-positive secretory vesicles and is required for neural development in zebrafish. In young neurons, BICDR-1 accumulates Rab6 secretory vesicles around the centrosome, restricts anterograde secretory transport and inhibits neuritogenesis. Later during development, BICDR-1 expression is strongly reduced, which permits anterograde secretory transport required for neurite outgrowth. These results indicate an important role for BICDR-1 as temporal regulator of secretory trafficking during the early phase of neuronal differentiation.

SIGNOR-266877

P04637

Q13464

0

phosphorylation

up-regulates quantity

0.409

Besides, ROCK1 phosphorylated p53 at ser15 to up-regulate its protein level.

SIGNOR-280108

P48735

Q9NXA8

0

catalytic activity

up-regulates activity

0.409

Here, we report that SIRT5 desuccinylates and deglutarylates isocitrate dehydrogenase 2 (IDH2) and glucose-6-phosphate dehydrogenase (G6PD), respectively, and thus activates both NADPH-producing enzymes.

SIGNOR-261212

P50222

P15863

0

binding

up-regulates activity

0.409

We show that Mox1 and Mox2 proteins are capable of interacting with Pax1 and Pax3. We propose that the Mox family of homeodomain proteins participates in the molecular signaling network regulating the diverse events of somite development through the physical interaction with the Pax1 and Pax3 members of the Pax family.

SIGNOR-222232

P35222

P36888

0

phosphorylation

up-regulates activity

0.409

Endogenous beta-catenin co-immunoprecipitated with endogenous activated FLT3, and recombinant activated FLT3 directly phosphorylated recombinant beta-catenin. Finally, FLT3 inhibitor decreased tyrosine phosphorylation of beta-catenin in leukemia cells obtained from FLT3-ITD-positive AML patients. These data demonstrate that FLT3 activation induces beta-catenin tyrosine phosphorylation and nuclear localization, and thus suggest a mechanism for the association of FLT3 activation and beta-catenin oncogeneic signaling in AML.

SIGNOR-260124

O43609

Q06124

0

dephosphorylation

down-regulates

0.409

These results identify sprouty proteins as in vivo targets of corkscrew/shp-2 tyrosine phosphatases and show how corkscrew/shp-2 proteins can promote rtk signaling by inactivating a feedback inhibitor.

SIGNOR-144547

P19174

P63211

0

binding

up-regulates

0.409

Furthermore, this work suggested that the gbetagamma subunits released upon gi activation activated phospholipase c-gamma (plc-gamma) to produce inositol 3 phosphate (ip3) which would subsequently increase intracellular ca2+ abundance.

SIGNOR-199144

Q9H2G9

Q9NTX7

0

ubiquitination

down-regulates quantity by destabilization

0.409

Here, we identify RNF146, a RING-domain E3 ubiquitin ligase, as a positive regulator of Wnt signalling. RNF146 promotes Wnt signalling by mediating tankyrase-dependent degradation of axin. Mechanistically, RNF146 directly interacts with poly(ADP-ribose) through its WWE domain, and promotes degradation of PARsylated proteins. Using proteomics approaches, we have identified BLZF1 and CASC3 as further substrates targeted by tankyrase and RNF146 for degradation.

SIGNOR-263340

Q7L591

P07948

0

phosphorylation

up-regulates activity

0.409

An adaptor protein Dok-3 mediates the suppressive function of LYN. The Dok-3 phosphorylated by LYN upon BCR stimulation forms a complex with GRB2, which allows it to enter into the signalosome and associate with activation of SHIP protein. This translocation facilitates the efficient inhibition of PLCc2 and SYK from activation, subsequently resulting in the suppression of downstream Ca2+ signaling.

SIGNOR-268447

Q9NS23

P11802

0

phosphorylation

down-regulates

0.409

This skp2-dependent destruction of rassf1a requires phosphorylation of the latter on serine-203 by cyclin d-cyclin-dependent kinase 4.

SIGNOR-159849

Q01484

O00533

0

relocalization

up-regulates quantity

0.409

Neurofascin, L1, NrCAM, NgCAM, and neuroglian are membrane-spanning cell adhesion molecules with conserved cytoplasmic domains that are believed to play important roles in development of the nervous system. This report presents biochemical evidence that the cytoplasmic domains of these molecules associate directly with ankyrins, a family of spectrin-binding proteins located on the cytoplasmic surface of specialized plasma membrane domains.

SIGNOR-266722

P00533

P42685

0

phosphorylation

down-regulates activity

0.409

Furthermore, Rak/Frk inhibited mutant EGFR phosphorylation at an activating site and dramatically decreased the levels of EGFR\u0394747-749/A750P from the plasma membrane.|Taken together, the results suggest that Rak and Frk inhibits EGFR signaling in cancer cells and has elevated activity against EGFR exon 19 mutants.

SIGNOR-279177

Q12888

Q96GD4

0

phosphorylation

up-regulates activity

0.409

Here we report for the first time that tumor suppressor p53-binding protein 1 (53BP1) is phosphorylated at serine 1342 (S1342) by Aurora kinase B both in vitro and in human cells, which is required for optimal recruitment of 53BP1 at kinetochores.

SIGNOR-264411

Q14457

P19484

0

transcriptional regulation

up-regulates quantity by expression

0.409

As expected, we found that glucose deprivation induced the binding of TFEB (Figure S4C) and ACSS2 (Figure S4D) to the promoter regions of MAP1LC3B, ATG3, and WIPI-1 as well as mRNA (Figure 3H) and protein (Figure 3I) expression of these genes;

SIGNOR-276558

P60709

Q9Y4I1

0

binding

up-regulates activity

0.409

Myosin Va regulates exocytosis of large dense-core vesicles (LDCVs). interestingly, inhibition of myosin Va potentiates LDCV exocytosis to the same extent as F-actin depolymerization does, suggesting that myosin Va cooperates with the actin cytoskeleton to impede or control LDCV exocytosis

SIGNOR-269280

Q9Y365

P68400

0

phosphorylation

down-regulates

0.409

Interestingly, hypotonic extracts prepared from hek293t cells expressing the serine to alanine mutant exhibited increased lipid transfer activity compared with those from wild-type stard10-expressing cells, suggesting that, in a cellular context, phosphorylation on serine 284 negatively regulates stard10 activity

SIGNOR-155740

P26678

Q13976

0

phosphorylation

up-regulates activity

0.409

Phosphorylation of PLB by PKA or cGKI at Ser 16 relieves the inhibition of SERCA2a and results in increased contractility through enhanced Ca 2+ i reuptake into the SR.

SIGNOR-279269

Q68CZ2

P12931

0

phosphorylation

up-regulates

0.408

Tyrosines in the sh2 domain contribute to the biological activity of tensin-3, and phosphorylation of these tyrosines can regulate ligand binding. tensin-3 is a src substrate

SIGNOR-187843

Q9P2Y5

P42345

0

phosphorylation

up-regulates activity

0.408

MTOR phosphorylates UVRAG at serine 550 and serine 571

SIGNOR-276919

Q13469

P48454

0

dephosphorylation

up-regulates activity

0.408

NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity

SIGNOR-248512

Q13507

Q13976

0

phosphorylation

down-regulates

0.408

The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.

SIGNOR-142961

Q13507-3

Q13976

0

phosphorylation

down-regulates

0.408

The present study demonstrates that human trpc3 expressed in hek293 cells forms store-operated ca2+ influx channels, the activity of which is inhibited by pkg. The inhibition is due to a direct phosphorylation of pkg on trpc3 channels at position t11 and s263.

SIGNOR-142957

Q86UR1

P12931

0

phosphorylation

up-regulates

0.408

Here, we show that the interaction of noxa1 and tks proteins is dependent on src activity. Interestingly, the abolishment of src-mediated phosphorylation of tyr110 on noxa1 and of tyr508 on tks4 blocks their binding and decreases nox1-dependent ros generation.

SIGNOR-168545

P07101

Q00535

0

phosphorylation

up-regulates activity

0.408

In addition, we demonstrate that co-expression of cdk5 and its regulatory activator p35 with TH increases the stability of TH.|We show that cdk5 phosphorylates TH at serine 31 and that this phosphorylation is associated with an increase in total TH activity.

SIGNOR-279022

Q13541

Q9H0H3

0

binding

down-regulates quantity by destabilization

0.408

We identified the KLHL25-CUL3 complex as the E3 ubiquitin ligase, which targets hypophosphorylated 4E-BP1. Thus, the activity of eIF4E is under homeostatic control via the regulation of the levels of its repressor protein 4E-BP1 through ubiquitination.

SIGNOR-272049

Q14344

Q96RI0

0

binding

up-regulates

0.408

Upon proteolysis, the newly formed n terminus acts as a tethered ligand that activates the receptor and initiates signaling cascades through multiple g proteins (galfaq, galfai, and galfa12/13)

SIGNOR-196015

P17275

Q96J02

0

polyubiquitination

down-regulates quantity by destabilization

0.408

Itch promotes Ub conjugation to JunB Molecularly, Itch associated with and induced ubiquitination of JunB, a transcription factor that is involved in TH2 differentiation. However, in Itch−/− T cells under the same conditions, degradation of JunB was markedly delayed.

SIGNOR-272619

Q01130

Q13627

0

phosphorylation

down-regulates activity

0.408

Dyrk1A inhibits SC35\u2032s activity to promote tau exon 10 inclusion.|Dyrk1A interacts with and phosphorylates SC35 and inhibits its activity to promote tau exon 10 inclusion.

SIGNOR-278307

Q01453

P16144

0

binding

up-regulates activity

0.408

PMP22 is in a complex with α6β4 integrin and laminin. PMP22 and β4 integrin are in a complex in a variety of cell types. The interaction with the integrins provides PMP22 with the ability to modulate the cell–ECM communications, as well as intracellular events. Signaling between the ECM and the intracellular compartment is essential for SC myelination, as well as cellular differentiation and motility, in general. The identification of PMP22 as a binding partner for an integrin signaling complex provides a major step toward understanding the role of this disease-linked molecule in the nervous system and in non-neural cell types.

SIGNOR-251896

P50148

Q9NPG1

0

binding

up-regulates

0.408

Gpcrs signal through four relatively small families of galfa proteins (galfas, galfai/o, galfaq, and galfa12/13), and if fzd receptors are classic gpcrs, they should signal through one of these four galfa families.

SIGNOR-122895

Q14524

Q13554

0

phosphorylation

up-regulates activity

0.408

Among the sites identified, only six were previously suggested to be the targets for specific kinases using in silico and/or in vitro analyses: S36 and S525 were attributed to the regulation by PKA; S484 and S664 were assigned to the serum- and glucocorticoid-inducible kinase 3 (SGK3); and S516 and S571 were ascribed to CaMKII (reviewed in Marionneau and Abriel, 2015). In marked contrast, several previously described phosphorylation sites were not detected in the present study, including the PKA-dependent S528, the CaMKII-associated T594, the PKC-dependent S1506, the adenosine monophosphate–activated protein kinase (AMPK)–dependent T101 (Liu et al., 2019), and the six Fyn-dependent tyrosines (Ahern et al., 2005; Iqbal et al., 2018).|The simplest interpretation of these findings is that these three phosphorylation clusters, at positions S457-S460, S483-T486, and S664-S671, are likely involved in regulating the basal and/or gating properties of native cardiac NaV1.5 channels. Conversely, the other phosphorylation sites, with lower stoichiometries, may play spatially or temporally distinct roles in the physiological or more pathophysiological regulation of channel expression or gating. | Remarkably, this MS analysis also revealed that the vast majority of identified phosphorylation sites (at least 26) are clustered, suggesting concomitant phosphorylation and roles in regulating channel expression and/or function. Unexpectedly, however, except for S664, S667, and S671, no apparent effects of phosphomimetic or phosphosilent mutations were observed on heterologously expressed (in HEK-293 cells) NaV1.5

SIGNOR-275773

Q9H492

Q8IXH6

0

binding

up-regulates

0.408

Tp53inp2 is a scaffold protein that recruits lc3 and/or lc3-related proteins to the autophagosome membrane by interacting with the transmembrane protein vmp1

SIGNOR-182614

Q9BV73

Q96CN5

0

binding

up-regulates activity

0.408

Here, we show that LRRC45 is a centrosome linker that localizes at the proximal ends of the centrioles and forms fiber-like structures between them. Depletion of LRRC45 results in centrosome splitting during interphase. LRRC45 interacts with C-Nap1 and rootletin

SIGNOR-273703

P30291

P68400

0

phosphorylation

down-regulates quantity by destabilization

0.408

In the present study, we show that phosphorylation of S123 (pS123) by CDK promoted the binding of Wee1A to beta-TrCP through three independent mechanisms. S123 phosphorylation creates a PBD-binding motif and accelerates S53 phosphorylation by Plk1.

SIGNOR-276038

P00441

Q16236

0

transcriptional regulation

up-regulates quantity by expression

0.408

BTG2 was found to up-regulate expression of antioxidant enzymes known to be regulated by NFE2L2, including catalase, SOD1, and SOD2

SIGNOR-254653

Q8TDD2

Q16539

0

phosphorylation

up-regulates activity

0.408

We therefore propose that Osterix binds to Sp1 sequences on target gene promoters and that its phosphorylation by p38 enhances recruitment of coactivators to form transcriptionally active complexes

SIGNOR-255791

O14490

Q00535

0

phosphorylation

down-regulates quantity by destabilization

0.408

Taken together, these sets of data suggest that Abeta triggers the phosphorylation of GKAP by cdk5 at the serine residues S77 and S111 that in turn are crucial for GKAP degradation.

SIGNOR-279153

P20226

Q12947

0

binding

up-regulates activity

0.408

The human forkhead protein FREAC-2 contains two functionally redundant activation domains and interacts with TBP and TFIIB.

SIGNOR-220373

Q92911

Q06710

0

transcriptional regulation

up-regulates quantity by expression

0.408

Pax8 has an essential role in thyroid organogenesis and differentiation, being the main mediator of thyroid gene transcription, including the NIS gene.

SIGNOR-251990

Q16539

P35813

0

dephosphorylation

down-regulates activity

0.408

Moreover, when expressed in mammalian cells, pp2ca inhibited the activation of the p38 and jnk cascades induced by environmental stresses. Both in vivo and in vitro observations indicated that pp2ca dephosphorylated and inactivated mapkks (mkk6 and sek1) and a mapk (p38) in the stress-responsive mapk cascades. Furthermore, a direct interaction of pp2ca and p38 was demonstrated by a co-immunoprecipitation assay

SIGNOR-59618

P30679

P41231

0

binding

up-regulates activity

0.408

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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257031

P36888

P43405

0

phosphorylation

up-regulates activity

0.407

Only two mutants, FLT3-KD (V5) Y768A and Y955A, were resistant to SYK-mediated FLT3 phosphorylation, suggesting that SYK directly phosphorylates FLT3 at sites Y768 and Y955 ( ).|SYK Enhances FLT3 WT and Mutant Activation by Phosphorylation of Residues Y768 and Y955.

SIGNOR-278431

P15927

Q9NUX5

0

binding

down-regulates activity

0.407

The current model for how telomeres repress ATR signaling proposes that POT1/TPP1 prevents the binding of RPA to the single-stranded telomeric DNA

SIGNOR-263324

Q15717

P06493

0

phosphorylation

down-regulates activity

0.407

Cdk1 inhibition promoted a cytoplasmic accumulation of HuR, while a predominately nuclear localization of HuR was observed under conditions of high Cdk1 activity.|Kim et al. further showed that Cdk1-dependent Ser-202 phosphorylation of HuR was essential for 14-3-3\u03b8 binding to HuR.

SIGNOR-279014

P29597

P08575

0

dephosphorylation

down-regulates activity

0.407

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling|these results show that CD45 dephosphorylates functionally important tyrosine residues. It should be noted that, as with our phosphatase assays in vitro, Tyr 1022 and Tyr 1023 of JAK1, Tyr 1007 and Tyr 1008 of JAK2, and Tyr 1054 and Tyr 1055 of Tyk2 are indeed hyperphosphorylated in cd45-deficient cells

SIGNOR-248357

Q92558

P12931

0

phosphorylation

up-regulates

0.407

The wave/scar proteins regulate actin polymerisation at the leading edge of motile cells via activation of the arp2/3 complex in response to extracellular cues.Src-dependent phosphorylation of scar1 promotes its association with the arp2/3 complex

SIGNOR-142724

O95837

Q9UNW8

0

binding

up-regulates activity

0.407

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 ≥ -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 ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0.

SIGNOR-257396

P63092

Q13255

0

binding

up-regulates activity

0.407

MGluRs are members of the G-protein-coupled receptor (GPCR) superfamily, the most abundant receptor gene family in the human genome. GPCRs are membrane-bound proteins that are activated by extracellular ligands such as light, peptides, and neurotransmitters, and transduce intracellular signals via interactions with G proteins. The resulting change in conformation of the GPCR induced by ligand binding activates the G protein, which is composed of a heterotrimeric complex of α, β, and γ subunits.

SIGNOR-264077

P42680

Q08881

0

phosphorylation

up-regulates

0.407

Tec family protein tyrosine kinases (tfks) play a central role in hematopoietic cellular signaling. Initial activation takes place through specific tyrosine phosphorylation situated in the activation loop. Further activation occurs within the sh3 domain via a transphosphorylation mechanism. Here, we could confirm that y223 is the only site in the btk-sh3 domain being detectably phosphorylated

SIGNOR-98090

P52732

Q8TDX7

0

phosphorylation

up-regulates activity

0.407

NEK7 regulates these processes in part through phosphorylation of the kinesin Eg5/KIF11, promoting its accumulation on microtubules in distal dendrites.

SIGNOR-273890