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  • Original Paper
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SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF β-receptor

Oncogene volume 21, pages 1870–1875 (2002)Cite this article

Abstract

We have previously shown that the binding site for GTPase activating protein of Ras (RasGAP) in the PDGF β-receptor, Tyr771, is phosphorylated to a much lower extent in the heterodimeric configuration of PDGF α- and β-receptors, compared to the PDGF β-receptor homodimer. The decreased recruitment of the RasGAP to the receptor leads to prolonged activation of the Ras/MAP kinase pathway, which could explain the increase in mitogenicity seen upon induction of heterodimers. The molecular mechanism underlying these differences was investigated. We could show that the loss of phosphorylation of Tyr771 was dependent on presence of intact binding sites for the protein tyrosine phosphatase SHP-2 on the PDGF β-receptor. Thus, in PDGF receptor mutants in which binding of SHP-2 was lost, a higher degree of phosphorylation of Tyr771 was seen, while other phosphorylation sites in the receptor remained virtually unaffected. Thus, SHP-2 appears to play an important role in modulating phosphorylation of Y771, thereby controlling RasGAP recruitment and Ras/MAP kinase signaling in the heterodimeric configuration of the PDGF receptors.

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Acknowledgements

Lars Rönnstrand holds a position as Senior Researcher funded by the Swedish Research Council.

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

    Simon Ekman, Anders Kallin, Ulla Engström, Carl-Henrik Heldin & Lars Rönnstrand

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  1. Simon Ekman
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  2. Anders Kallin
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  3. Ulla Engström
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  4. Carl-Henrik Heldin
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  5. Lars Rönnstrand
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Correspondence to Lars Rönnstrand.

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Ekman, S., Kallin, A., Engström, U. et al. SHP-2 is involved in heterodimer specific loss of phosphorylation of Tyr771 in the PDGF β-receptor. Oncogene 21, 1870–1875 (2002). https://doi.org/10.1038/sj.onc.1205210

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