SHP-2 binds to Tyr763 and Tyr1009 in the PDGF β-receptor and mediates PDGF-induced activation of the Ras/MAP kinase pathway and chemotaxis
1999 (English)In: Oncogene, ISSN 0950-9232, Vol. 18, no 25, 3696-3702 p.Article in journal (Refereed) Published
Activation of the beta-receptor for platelet-derived growth factor (PDGF) by its ligand leads to autophosphorylation on a number of tyrosine residues. Here we show that Tyr763 in the kinase insert region is a novel autophosphorylation site, which after phosphorylation binds the protein tyrosine phosphatase SHP-2. SHP-2 has also previously been shown to bind to phosphorylated Tyr1009 in the PDGF beta-receptor. Porcine aortic endothelial (PAE) cells transfected with a PDGF beta-receptor in which Tyr763 and Tyr1009 were mutated to phenylalanine residues failed to associate with SHP-2 after ligand stimulation. Moreover, PDGF-BB-induced Ras GTP-loading and Erk2 activation were severely compromised in the receptor mutant. Whereas the mitogenic response to PDGF-BB remained at the same level as in cells expressing wild-type PDGF beta-receptor, chemotaxis induced by PDGF-BB was significantly decreased in the case of the Y763F/Y1009F mutant cells, suggesting an important role for SHP-2 in chemotactic signaling.
Place, publisher, year, edition, pages
Stockton Press , 1999. Vol. 18, no 25, 3696-3702 p.
PDGF beta-receptor; SHP-2; chemotaxis; Ras/MAP kinase pathway
IdentifiersURN: urn:nbn:se:uu:diva-91007PubMedID: 10391677OAI: oai:DiVA.org:uu-91007DiVA: diva2:163570