Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor

S. A. Courtneidge, R. Dhand, D. Pilat, G. M. Twamley, M. D. Waterfield, M. F. Roussel

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

The receptor for the macrophage colony stimulating factor-1 (CSF-1R) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity. CSF-1 stimulation promotes the growth of cells of the macrophage lineage and of fibroblasts engineered to express CSF-1R. We show that CSF-1 stimulation resulted in activation of three Src family kinases, Src, Fyn and Yes. Concomitant with their activation, all three Src family kinases were found to associate with the ligand-activated CSF-1 receptor. These interactions were also demonstrated in SF9 insect cells co-infected with viruses encoding the CSF-1 receptor and Fyn, and the isolated SH2 domain of Fyn was capable of binding the CSF-1R in vitro. Analysis of mutant CSF-1Rs revealed that the 'kinase insert' (KI) domain of CSF-1R was not required for interactions with Src family kinases, but that mutation of one of the receptor autophosphorylation sites, Tyr809, reduced both their binding and enzymatic activation. Because fibroblasts expressing this receptor mutant are unable to form colonies in semi-solid medium or to grow in chemically defined medium in the presence of CSF-1, the Src family kinases may play a physiological role in the mitogenic response to CSF-1.

Original languageEnglish (US)
Pages (from-to)943-950
Number of pages8
JournalEMBO Journal
Volume12
Issue number3
StatePublished - Jan 1 1993

Keywords

  • CSF-1 receptor
  • Colony stimulating factor
  • Protein tyrosine kinases
  • Src family kinases
  • Src homology-2 (SH2) domains

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Courtneidge, S. A., Dhand, R., Pilat, D., Twamley, G. M., Waterfield, M. D., & Roussel, M. F. (1993). Activation of Src family kinases by colony stimulating factor-1, and their association with its receptor. EMBO Journal, 12(3), 943-950.