• As we mapped and mutated phosphorylation sites in the platelet-derived growth factor (PDGF) receptor, we found a dramatic difference in interactions of three tyrosines in the `kinase-insert' region. (the-scientist.com)
  • c-Met and receptor originated from nantes (RON) are structurally related transmembrane phosphotyrosine kinase receptors. (oncotarget.com)
  • c-Met and RON form both activated homodimers and heterodimers with themselves and other families of phosphotyrosine kinase receptors. (oncotarget.com)
  • The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
  • The PI 3-kinase inhibitor LY294002 also prevents apoptotic cell phagocytosis but has no effect on the accumulation of F actin and phosphotyrosine. (nih.gov)
  • Previous experiments have not been able to elucidate whether interactions with membrane-tethered proteins primarily control PI3Kβ localization versus directly modulate lipid kinase activity. (elifesciences.org)
  • To address this gap in our understanding of PI3Kβ regulation, we established an assay to directly visualize and decipher how three binding interactions regulate PI3Kβ when presented to the kinase in a biologically relevant configuration on supported lipid bilayers. (elifesciences.org)
  • We propose that the resulting disruption of native TM interactions disrupts the conformation of the kinase domain, inhibiting EGFR's ability to send migratory cell signals. (biorxiv.org)
  • The tensin family member cten (C-terminal tensin like) is an Src homology 2 (SH2) and phosphotyrosine binding domain-containing focal adhesion molecule that may function as a tumor suppressor. (rupress.org)
  • Adam Kashishian (Fred Hutchinson Cancer Research Center, Seattle): "The question of the specificity of Src homology 2 (SH2) domain/phosphotyrosine interactions has been an important one since the ability of the SH2 domains to bind phosphotyrosine- containing peptides was first shown. (the-scientist.com)
  • SH2 (Src homology region 2) and PTB (phosphotyrosine-binding) domains are small protein modules that mediate protein-protein interactions involved in many signal transduction pathways. (chemdiv.com)
  • This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. (antikoerper-online.de)
  • To mediate these processes, the extracellular ligand binding region of EGFR senses environmental cues via interactions with one of its 7 known ligands, of which epidermal growth factor (EGF) is the most well characterized ( 2 , 3 ). (biorxiv.org)
  • 1998). In both examples, the high affinity ligands can compete with the intramolecular interactions and release the catalytic domains for their in vivo targets. (lu.se)
  • SH2 domain-mediated interactions represent a crucial step in transmembrane signaling by receptor tyrosine kinases. (ufoscience.org)
  • By site-directed mutagenesis, we have identified several amino acid residues on cten and DLC-1 that are essential for this interaction. (rupress.org)
  • The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
  • The selectivity of an individual SH2 domain is not sharply defined, and a range of residues is typically tolerated at each site following the phosphotyrosine. (lu.se)
  • Residues from αB-helix and the EF and BG-loops are involved in binding of side chains C-terminal to phosphotyrosine in the ligand. (lu.se)
  • Thus, our discovery of the role of functional interaction between intracellular signaling pathways mediated by calcium ions (Ca 2+) and cyclic adenosine monophosphate (cAMP) (Ca 2+ /cAMP signaling interaction) in these cellular responses, opened a great avenue for the development of new antitumor therapeutic strategies. (researchgate.net)
  • We report that cten binds to another tumor suppressor, deleted in liver cancer 1 (DLC-1), and the SH2 domain of cten is responsible for the interaction. (rupress.org)
  • WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: the proline glycine and methionine-rich motif. (embl.de)
  • They are able to bind specific motifs containing a phosphorylated tyrosine residue, propagating the signal downstream by promoting protein-protein interactions and/or modifying enzymatic activities. (eu.org)
  • The CCM2 phosphotyrosine binding (PTB) domain is necessary for a canonical interaction with NPxY motifs within CCM1. (unc.edu)
  • It contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. (avivasysbio.com)
  • SH2 domains recognize phosphotyrosine (pY) in the context of particular sequence motifs in receptor phosphorylation sites. (ufoscience.org)
  • By using machine learning and subsequent biochemical validation we detect ligand-dependent, non-canonical interaction of EGFR and Met. (nature.com)
  • In contrast, we were unable to identify electron density for hydrophobic fragments, confirming that hydrophobic interactions are important for inhibitor affinity but of minor importance for ligand recognition. (rcsb.org)
  • In addition to their role in assembling activated complexes, particular SH2 domains also form intramolecular interactions that regulate enzyme activity. (lu.se)
  • Phosphotyrosine interaction domain containing 1 is a protein that in humans is encoded by the PID1 gene. (wikipedia.org)
  • Unexpectedly, the interaction between DLC-1 and the cten SH2 domain is independent of tyrosine phosphorylation of DLC-1. (rupress.org)
  • Through a novel CCM2 PTB domain - Smurf1 HECT domain interaction, CCM2 recruits Smurf1 to specific locations at the plasma membrane where it specifically degrades RhoA. (unc.edu)
  • In yeast, this bridging involves interactions between the WW domains in the splicing factor PRP40 and a proline-rich domain in the branchpoint binding protein, BBP. (embl.de)
  • What determines the specificity of SH2 interactions with other molecules? (ufoscience.org)
  • non-canonical EGFR-Met interactions are implicated in resistance to anti-cancer drugs but have not been previously detected in drug-naïve cells. (nature.com)
  • We observed that PET1 behaves as a pH-responsive peptide that modulates the configuration of the EGFR TM through a direct interaction. (biorxiv.org)
  • We show that inhibition of Rho GTPases by Clostridium difficile toxin B prevents apoptotic cell phagocytosis and inhibits the accumulation of both F-actin and phosphotyrosine. (nih.gov)
  • To understand the full spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in differentiated brown adipocytes. (harvard.edu)
  • Although apoptotic cells are known to be efficiently phagocytosed by macrophages, the mechanisms whereby their interaction with the phagocytes triggers their engulfment have not been described in mammals. (nih.gov)
  • This presents a starting point for studies into the underlying mechanisms of AD including interactions with other AD-associated genes, like Rho1, Ankyrin, Tau and APP with the potential to identify new targets for treatment. (sdbonline.org)
  • The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
  • Mutations on DLC-1 perturb the interaction with cten and disrupt the focal adhesion localization of DLC-1. (rupress.org)
  • Figure 1 shows how the Ca 2+ /cAMP signaling interaction could be pharmacologically modulated by the combined use of the Ca 2+ channel blockers (CCB) and drugs that promote the increase of [cAMP] c (cAMP-enhancer compounds). (researchgate.net)
  • but with very few exceptions, these interactions have not been confirmed in vivo . (jneurosci.org)
  • A direct interaction between SAEC and MWCNT was confirmed by both internalization of MWCNT as well as an interaction at the cell periphery. (cdc.gov)
  • We previously reported that EphA5 receptor-ephrinA5 interactions within the ventromedial hypothalamus (VMH) influence counterregulatory hormone responses during acute hypoglycemia in nondiabetic rats. (diabetesjournals.org)
  • These data suggest that changes in ephrinA5/EphA5 interactions and synaptic plasticity within the VMH, a key glucose-sensing region in the brain, may contribute to the impairment in glucagon secretion and counterregulatory responses caused by recurrent hypoglycemia. (diabetesjournals.org)
  • Description: A sandwich ELISA kit for detection of Dual Adaptor Of Phosphotyrosine And 3-Phosphoinositides from Human in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (scalegen.com)
  • Cell lysates were then precipitated with Flag-specific antibodies (left panel) and blotted with antibodies specific for myc (top), phosphotyrosine 4G10 (middle), or Lnk (bottom). (jci.org)
  • Here, we report that primary murine bone marrow-derived macrophages (using alpha(v)beta(3) integrin for apoptotic cell uptake) extend lamellipodia to engulf apoptotic cells and form an actin cup where phosphotyrosine accumulates. (nih.gov)
  • A proteomic interaction screen with PISP/PDZK11 identified the calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. (harvard.edu)
  • In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)