Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

• DOI: 10.1128/mcb.13.11.6889
• Publication Date: 2015-10-06T00:36:48Z
• Authors: R Nishimura; W Li; A Kashishian; A Mondino; M Zhou; J Cooper; J Schlessinger
• Keywords: Platelet-Derived Growth Factor; 0303 health sciences; Binding Sites; Macromolecular Substances; Molecular Sequence Data; Becaplermin; Receptor Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-sis; Kidney; Epithelium; Phosphatidylinositol 3-Kinases; Phosphotransferases (Alcohol Group Acceptor); 03 medical and health sciences; Dogs; Mutagenesis, Site-Directed; Animals; Humans; Amino Acid Sequence; Phosphorylation; Phosphotyrosine; Cells, Cultured; Glutathione Transferase

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding for Src homology 2 (SH2) domains signaling molecules. This interaction appears to be a crucial step in mechanism by which receptor kinases relay signals downstream pathways. Nck is widely expressed protein consisting exclusively SH2 and SH3 domains, the overexpression causes cell transformation. It has been shown that various factors stimulate phosphorylation its association autophosphorylated receptors. A panel platelet-derived (PDGF) mutations at residues used identify site. Here we show mutation Tyr-751 PDGF beta-receptor eliminates both vitro living cells. Moreover, Y751F mutant failed mediate PDGF-stimulated intact phosphorylated also required phosphatidylinositol-3 receptor. Hence, p85 share site Competition experiments different phosphopeptides derived from suggest influenced around Tyr-751. Thus, single autophosphorylation able link two distinct domain-containing