• The N-terminus domain of LMP2A is tyrosine phosphorylated and associates with Src family protein tyrosine kinases (PTKs) as well as spleen tyrosine kinase (Syk). (wikipedia.org)
  • Receptor docking with molecules containing cytoplasmic tyrosine kinases is governed by Phosphorylation of ITAM motifs. (wikipedia.org)
  • In lymphoblastoid cell cultures, Syk tyrosine kinases have been found in LMP2A immunoprecipitates following in vitro kinase reactions followed by Syk antibody reimunnoprecipitation. (wikipedia.org)
  • Cytokine binding to the cell surface leads to phosphorylation of the receptor complex by receptor associated Janus kinases (JAKs) at tyrosine residues. (nature.com)
  • Nuclear localized HER family receptor tyrosine kinases (RTKs) have been observed in primary tumor specimens and cancer cell lines for nearly two decades. (plos.org)
  • The ErbB/HER family of receptor tyrosine kinases (RTKs) consists of four family members: the epidermal growth factor receptor (EGFR/ErbB1), HER2 (ErbB2/Neu), HER3 (ErbB3), and HER4 (ErbB4). (plos.org)
  • Epidermal growth factor receptor (EGF R, also known as ErbB1 and HER1) is the founding member of the ErbB family of receptor tyrosine kinases. (rndsystems.com)
  • In recent years, the search for intracellular signaling integrator downstream of receptor tyrosine kinases provided valuable novel substrates. (springer.com)
  • Binding of IL-10 to the extracellular domain of IL-10R1 activates phosphorylation of the receptor-associated Janus tyrosine kinases, JAK1 and Tyk2. (nih.gov)
  • These kinases then phosphorylate specific tyrosine residues (Y446 and Y496) on the intracellular domain of the IL-10R1 chain. (nih.gov)
  • The trk receptors, a family of receptor tyrosine kinases including trkA, trkB, and trkC, serve as the principal signal-transducing receptors for the neurotrophins ( Barbacid, 1994 ). (jneurosci.org)
  • Protein phosphorylation is a reversible and dynamic post-translational modification that is governed by the opposing activities of protein phosphatases and kinases. (rndsystems.com)
  • Tyrosine kinases , including BTK, mediate phosphorylation of tyrosine residues on signaling pathway molecules and have roles in cell reproduction, differentiation, growth, metabolism, and apoptosis. (physiciansweekly.com)
  • Predikin now consists of two components: (i) PredikinDB, a database of phosphorylation sites that links substrates to kinase sequences and (ii) a Perl module, which provides methods to classify protein kinases, reliably identify substrate-determining residues, generate scoring matrices and score putative phosphorylation sites in query sequences. (biomedcentral.com)
  • Protein kinases, the enzymes responsible for protein phosphorylation, make up almost 2% of protein-encoding genes in the human genome [ 1 ] and an estimated 30-50% of human proteins are phosphorylated [ 2 ]. (biomedcentral.com)
  • Crystal structures of protein kinases with bound substrate peptides show that substrate residues at positions -3 to +3 relative to the phosphorylated serine, threonine or tyrosine residue adopt an extended conformation and bind to a pocket in the catalytic domain of the protein kinase [ 8 ]. (biomedcentral.com)
  • The degradative pathway of ErbB receptor tyrosine kinases stimulated by tyrosine kinase inhibitors appears to be chaperone mediated, and thus is similar to the pathways activated by the heat shock protein 90 (Hsp90) antagonist geldanamycin and by stress-induced mechanisms. (lclabs.com)
  • Drug-induced ubiquitylation and degradation of ErbB receptor tyrosine kinases: implications for cancer therapy. (lclabs.com)
  • Activation of receptor tyrosine kinases in these tumour areas by growth factors expressed by surrounding stromal cells phosphorylate β-catenin at tyrosine residues, which is thought to increase β-catenin nuclear translocation and tumour invasiveness. (eur.nl)
  • The c-Jun-NH2-terminal kinases (JNKs) regulate cell death, generally through the direct phosphorylation of both pro- and anti-apoptotic substrates. (bvsalud.org)
  • [ 5 ] When CagA is translocated to epithelial cells, it induces cell-signaling pathways, following phosphorylation of tyrosine residues by host cell Scr kinases. (medscape.com)
  • If these residues are inaccessible to kinases, how do they get phosphorylated then? (lu.se)
  • FAK is activated by phosphorylation at specific tyrosine residues, which then stimulate downstream signaling including the ERK1/2 pathway, leading to a variety of cellular responses. (techscience.com)
  • However, it is recognised that for many protein kinase families, particularly those that phosphorylate Ser/Thr residues, peptide specificity is the major factor that determines substrate specificity. (biomedcentral.com)
  • Together, these data indicate that matrix stiffening promotes the phosphorylation of Src, and that Src interacts with activated FAK to phosphorylate tyrosine residues on the cytoplasmic tail of VE-cadherin, which regulate endothelial barrier junction integrity via the mediation of catenin attachment. (cornell.edu)
  • Phosphorylated tyrosine residues recruit various intracellular adaptor and effector molecules that result in the propagation of growth promoting signal transduction cascades [1] , [2] . (plos.org)
  • It not only inhibits tyrosine phosphorylation but also enhances ubiquitinylation and accelerates endocytosis and subsequent intracellular destruction of ErbB-2 molecules. (lclabs.com)
  • Thus, casein kinase II-catalyzed phosphorylation of IRS-1 may be a component of the intracellular insulin signaling cascade. (thermofisher.com)
  • Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
  • In addition, phosphorylation of other Tyr residues (Tyr-925, and Tyr-861) creates binding sites for SH2 domains of intracellular signaling molecules such as Src, PI3 kinase, and Grb2. (fishersci.com)
  • The domain contains tyrosine residues, phosphorylation of which regulates the function of the ATPase. (embl.de)
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
  • Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis. (bvsalud.org)
  • The capacitation associated tyrosine phosphorylation is greatly reduced in the presence of Src specific inhibitors (SU6656 and SKI606) in vivo. (umass.edu)
  • However, in vitro kinase activity of PKA showed no effect of Src inhibitors in the phosphorylation of the PKA specific substrate, kemptide. (umass.edu)
  • Furthermore, by adding various kinase inhibitors, we confirmed that the phosphorylation status of rpS3 was regulated by both Lyn and doxorubicin, and the phosphorylation of rpS3 by Lyn increased drug resistance in cells by upregulating p-glycoprotein translation. (bmbreports.org)
  • Immunologic and confocal microscopic evidence also suggested a transient but significant stimulation of tyrosine phosphorylation of Cav-1 in β-cells briefly (for 15 min) exposed to IL-1β that was markedly attenuated by three structurally distinct inhibitors of protein tyrosine phosphorylation. (diabetesjournals.org)
  • methylation at certain residues of histones can regulate gene expression [ 4 ], and glycosylation is responsible for targeting substrates and changing protein half-life [ 2 ]. (hindawi.com)
  • Two motifs that are centered on Y74 and Y85 are spaced 7 residues apart to form an immunoreceptor tyrosine-based activation motif (ITAM) commonly found in Fc receptors and signal molecules of B-cell and T-cell receptors. (wikipedia.org)
  • This process leads to the activation of each receptors' tyrosine kinase and the subsequent phosphorylation of tyrosine residues located on their C-terminal tails. (plos.org)
  • Canertinib alkylates a cysteine residue specific to ErbB receptors. (lclabs.com)
  • Focal Adhesion Kinase (FAK) is a cytoplasmic tyrosine kinase that colocalizes with integrins in focal adhesions. (fishersci.com)
  • Renin activates the renin-angiotensin system by using its endopeptidase activity to cleave the peptide bonds between leucine and valine residues in angiotensinogen, [11] produced by the liver , to yield angiotensin I , which is further converted into angiotensin II by ACE , the angiotensin-converting enzyme primarily within the capillaries of the lungs. (wikipedia.org)
  • While the phosphorylation of tyrosine residues in the immunoreceptor tyrosine-based activation motifs (ITAMs) of Cd3 and the inducible interaction between Cd3 and Zap70 remained largely unaffected, the abundance of activated Zap70 dropped with decreasing peptide affinity. (nature.com)
  • Once phosphorylated, these tyrosine residues (and their flanking peptide sequences) serve as temporary docking sites for the latent transcription factor, STAT3 (signal transducer and activator of transcription-3). (nih.gov)
  • The second factor, termed peptide specificity, describes the interaction between amino acid residues in the catalytic domain of the protein kinase and the substrate residues that surround the phosphorylated residue. (biomedcentral.com)
  • Upon cytokine stimulation, STAT5 tyrosine phosphorylation (pYSTAT5) is transient, while in diverse neoplastic cells persistent overexpression and enhanced pYSTAT5 are frequently found. (nature.com)
  • Spry1, Spry2, and Spry4 but not Spry3 are induced transcriptionally and limit the duration and intensity mainly of ERK phosphorylation in response to growth factor (GF) stimulation (with the exception of EGF signaling). (springer.com)
  • Consequently, the phosphorylation and formation of the Lat signalosome was severely impaired under low-strength TCR stimulation. (nature.com)
  • Upon EGF stimulation of the cell, Eps15 becomes both phosphorylated on tyrosine residues and monoubiquitinated. (embl.de)
  • With centrality measures such as betweenness centrality, degree centrality, and closeness centrality, we observed a few important residues that significantly contribute to the conformational change of c-Src tyrosine kinase for the different time steps. (intechopen.com)
  • The expression of a mutated hyperactive gain-of-function (GOF) STAT5 without O-GlcNAcylation resulted in decreased tyrosine phosphorylation, oligomerization and transactivation potential and complete loss of oncogenic transformation capacity. (nature.com)
  • Results from these analyses demonstrated that the C-terminal domain of HER3 (CTD, amino acids distal to the tyrosine kinase domain) contained potent transactivation potential. (plos.org)
  • In this study, we examined the effects of FAK point mutations at tyrosine residues (Y397, Y925, Y861, and Y576/7) on osteogenic differentiation of human mesenchymal stem cells exposed to collagen I and cyclic tensile strain. (techscience.com)
  • Furthermore, we demonstrated that membrane type-one matrix metalloproteinase activity inhibition can nullify the effect that matrix stiffening has on vascularization ex ovo, and that inhibiting the phosphorylation of FAK tyrosine residue 397 (Y397) can alleviate stiffness-induced hyperpermeability in vitro and ex ovo. (cornell.edu)
  • These experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling. (nih.gov)
  • MAPK3 signaling exerts its effects through phosphorylation of downstream targets. (creativebiomart.net)
  • DOK3 interacted with CARD11 and decreased its phosphorylation in T cells by recruiting the catalytic subunit of protein phosphatase 4, thereby dampening downstream signaling. (bvsalud.org)
  • Residues for Syk binding have been discovered by inducing point mutations in Y74F and Y85F point. (wikipedia.org)
  • Expression of phosphorylation-defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation. (uci.edu)
  • Three sequential phosphorylation events on specific residues of p27, regulate the activity of these complexes and ultimately control cell cycle proliferation or arrest. (lu.se)
  • Inhibition of the kinase domain is halted through binding of the Ras-binding domain, or residues 155-227 of the protein, to the Ras-GTP effector domain. (news-medical.net)
  • In order to become active, the CR3 kinase domain must be converted to its active form by phosphorylation of the activation loop. (news-medical.net)
  • c-Src tyrosine kinase consists of the N-terminal unique region, the Src homology 3 (SH3), SH2, linker, kinase domain, and the regulatory C-terminal tail. (intechopen.com)
  • 7 The JAKs also trigger the activation and tyrosine phosphorylation of STAT5, causing parallel dimerization, nuclear translocation and tetramerization of STAT5. (nature.com)
  • This is consistent with reports that the slow phosphorylation of tyrosine residues of the Lat adaptor associates with recruitment and activation of the phospholipase Plcγ1, thereby constituting an important kinetic bottleneck for ligand discrimination 11 . (nature.com)
  • For example, cell adhesion to a fibronectin substratum involves concurrent activation of Src and phosphorylation of the FAK activation loop. (fishersci.com)
  • Notably, the first two post-translational modifications, which are required for the initial activation of these complexes, occur on solvent inaccessible (i.e., buried) tyrosine residues. (lu.se)
  • Phosphorylation at Tyr 1068 allows binding of the SH2 domain of the cytosolic adaptor Grb2. (rndsystems.com)
  • Thus, FAK activity is regulated by a complex set of phosphorylation sites, and thisphospho-regulation could be important for cell motility, cell growth, cytoskeletal organization, and adhesion-dependent cell survival. (fishersci.com)
  • STAT3 binds to these sites via its SH2 (Src homology 2) domain, and is, in turn, tyrosine-phosphorylated by the receptor-associated JAKs. (nih.gov)
  • An in vitro immunocomplex kinase assay indicated that the rpS3 protein acts as a substrate for Lyn, which phosphorylates the Y167 residue of rpS3. (bmbreports.org)
  • More generally, bioinformatics analyses have shown that ~15% of all phosphorylated residues are buried in the non-phosphorylated state, suggesting that transient exposure might be a general mechanism involved in protein regulation. (lu.se)
  • Consequently, amino acid variations through changing the type of residues of the target sites or key flanking residues could directly or indirectly influence PTM of protein and bring about a detrimental effect on protein function. (deepdyve.com)
  • Here, we used time-resolved high-throughput proteomic analyses to identify and quantify the phosphorylation events and protein-protein interactions encoding T cell ligand discrimination in antigen-experienced T cells. (nature.com)
  • We defined quantitative signatures of ligand affinity based on protein phosphorylation and protein-protein interaction (PPI) stoichiometry for critical molecular events associated with TCR signaling. (nature.com)
  • Because positively charged residues in NT-3 are important for binding to trkB, two negatively charged aspartate residues within the 11 amino acid motif of FL trkB were mutated to examine the role of electrostatic interactions on ligand binding. (jneurosci.org)
  • To investigate the conformational change of c-Src tyrosine kinase, we applied network analysis to time series of correlation among residues. (intechopen.com)
  • The time series of correlation between residues during the conformational change generated by targeted molecular dynamic simulation. (intechopen.com)
  • Overexpression of an inactive mutant of Cav-1 lacking the tyrosine phosphorylation site (Y14F) or an siRNA-mediated Cav-1 knock down also resulted in marked attenuation of IL-1β-induced iNOS gene expression and NO release from these cells, thus further implicating Cav-1 in this signaling cascade. (diabetesjournals.org)
  • Here we provide the first evidence to suggest that tyrosine phosphorylation of Cav-1 and subsequent interaction among members of the Ras signaling pathway within the membrane lipid microdomains represent early signaling mechanisms of IL-1β in β-cells. (diabetesjournals.org)
  • Different responses, e.g. antiviral versus antiproliferative responses, to type I IFNs subtypes have been studied and proximal signaling, such as STAT phosphorylation, does not appear to correlate with the outcome. (wikidoc.org)
  • This study investigates the relevance of β-catenin tyrosine phosphorylation for Wnt signalling and intestinal tumorigenesis in vivo. (eur.nl)
  • Results: This study provided in vivo evidence that β-cateninE654 is characterised by reduced affinity for cadherins, increased signalling and strongly increased phosphorylation at serine 675 by protein kinase A (PKA). (eur.nl)
  • Major research interests are cancer proteomics, focusing on the secretome, tumoral dynamics, quantitative proteomics, protein phosphorylation, and the stoichiometry of ubiquitination and acetylation. (hupo.org)
  • Although tyrosine phosphorylation of Eps15 has been implicated in EGF receptor internalization, the function of Eps15 ubiquitination is not known. (embl.de)
  • These two iso forms of LMP2 only differ in that LMP2A contains an extra 119 residue N-terminal domain encoded in exon 1. (wikipedia.org)
  • The method, named Predikin, identifies key conserved substrate-determining residues in the kinase catalytic domain that contact the substrate in the region of the phosphorylation site and so determine the sequence surrounding the phosphorylation site. (biomedcentral.com)
  • The heptapeptide sequence from -3 to +3 that best binds to the pocket is determined by the physicochemical nature of the residues in the catalytic domain that line the pocket and contact the substrate. (biomedcentral.com)
  • Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. (rupress.org)
  • Here we demonstrate for the first time that MAVS undergoes extensive tyrosine phosphorylation upon viral infection, indicating that MAVS phosphorylation might play an important role in MAVS function. (nih.gov)
  • c-Src (cellular Src), encoded by Src gene, is a non-receptor tyrosine kinase first isolated as the normal cellular homolog to the potent avian sarcoma viral transforming oncogene v-Src [ 4 ]. (intechopen.com)
  • We sought to identify PKA phosphorylation sites in PLIN5 and assess their functional relevance in cultured cells and the livers of mice. (uci.edu)
  • Although low-affinity ligands induced phosphorylation of the Cd3 chains of the T cell receptor and the interaction of Cd3 with the Zap70 kinase as strongly as high-affinity ligands, they failed to activate Zap70 to the same extent. (nature.com)
  • By site-directed mutagenesis, we have identified several amino acid residues on cten and DLC-1 that are essential for this interaction. (rupress.org)