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  • Original Paper
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STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation

Oncogene volume 18, pages 3583–3592 (1999)Cite this article

Abstract

Activation of the platelet-derived growth factor (PDGF) receptor tyrosine kinase induces tyrosine phosphorylation of Signal Transducer and Activator of Transcription (STAT) proteins. Since the PDGF receptor also activates the Src tyrosine kinase, it is possible that Src mediates tyrosine phosphorylation of STATs in PDGF-treated cells. Consistent with a role for Src in STAT activation, we found that a PDGF receptor juxtamembrane tyrosine residue required for Src activation is necessary and sufficient for activation of STATs 1 and 3. To test the Src requirement further, we made other mutations in the PDGF receptor juxtamembrane region that increased or decreased Src binding. In epithelial and fibroblast cells, PDGF activated STAT1, 3 and 6 in the absence of detectable binding and activation of Src. In addition, PDGF induced c-myc RNA expression and DNA synthesis even though Src was not detectably activated. The activation of MAP kinase and the induction of c-fos gene expression both correlated with STAT but not Src activation by the receptor. We conclude that juxtamembrane tyrosine phosphorylation is necessary for both Src tyrosine kinase and STAT activation by the βPDGF receptor, but that both processes are regulated independently by this region.

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Acknowledgements

We thank A Kashishian for construction of PDGF receptor phosphorylation site mutants, L Claesson-Welsh for providing Y579F and Y581F mutant PDGF receptors and M Gilman for initiating the study of receptor activation of STATs and his continuing enthusiastic support. We thank D Bowen-Pope for providing PDGF-BB and S Courtneidge for cst.1 antibody. Human CSF-1 was a generous gift from Genetics Institute, Inc. Thanks to all members of the Cooper lab, R Klinghoffer, P Soriano, I Wolf, B Mai and E Wiley for helpful discussions and comments and J Torgerson for help with the manuscript. C Sachsenmaier was a recipient of an Erwin Schroedinger Auslandsstipendium of the Fonds zur Foerderung der Wissenschaftlichen Forschung, Austria. This work was supported by NIH grant CA54786.

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  1. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, 98109, Washington, USA

    Christoph Sachsenmaier & Jonathan A Cooper

  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, 11724, New York, USA

    Henry B Sadowski

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Sachsenmaier, C., Sadowski, H. & Cooper, J. STAT activation by the PDGF receptor requires juxtamembrane phosphorylation sites but not Src tyrosine kinase activation. Oncogene 18, 3583–3592 (1999). https://doi.org/10.1038/sj.onc.1202694

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