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  • Original Paper
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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

Oncogene volume 18, pages 3696–3702 (1999)Cite this article

Abstract

Activation of the β-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 β-receptor. Porcine aortic endothelial (PAE) cells transfected with a PDGF β-receptor in which Tyr763 and Tyr1009 were mutated to phenylalanine residues failed to associate with SHP-2 after ligand stimulation. Morover, 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 β-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.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research,Biomedical Centre, Box 595, Uppsala, S-751 24, Sweden

    Lars Rönnstrand, Ann-Kristin Arvidsson, Anders Kallin, Charlotte Rorsman, Ulf Hellman, Ulla Engström, Christer Wernstedt & Carl-Henrik Heldin

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  1. Lars Rönnstrand
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Rönnstrand, L., Arvidsson, AK., Kallin, A. et al. 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. Oncogene 18, 3696–3702 (1999). https://doi.org/10.1038/sj.onc.1202705

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