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  • The EMBO Journal (1997) 16, 2333 - 2341
  • doi:10.1093/emboj/16.9.2333

The Fc receptor big gamma-chain and the tyrosine kinase Syk are essential for activation of mouse platelets by collagen

A. Poole2,6, J.M. Gibbins1,6, M. Turner3,6, M.J. van Vugt4, J.G.J. van de Winkel4, T. Saito5, V.L.J. Tybulewicz3 and S.P. Watson1

  1. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
  2. Present address: Department of Pharmacology, University of Bristol,School of Medical Sciences, University Walk, Clifton, Bristol BS8 1TD, UK
  3. National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
  4. Deparment of Immunology, University Hospital Utrecht, PO Box 85.500, NL-3508 GA, Utrecht, The Netherlands
  5. Division of Molecular Genetics, Center for Biomedical Science, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan
  6. A.Poole, J.M.Gibbins and M.Turner contributed equally to this work

Received 25 November 1996; Revised 17 January 1997

Activation of mouse platelets by collagen is associated with tyrosine phosphorylation of multiple proteins including the Fc receptor gamma-chain, the tyrosine kinase Syk and phospholipase Cgamma2, suggesting that collagen signals in a manner similar to that of immune receptors. This hypothesis has been tested using platelets from mice lacking the Fc receptor gamma-chain or Syk. Tyrosine phosphorylation of Syk and phospholipase Cgamma2 by collagen stimulation is absent in mice lacking the Fc receptor gamma-chain. Tyrosine phosphorylation of phospholipase Cgamma2 by collagen stimulation is also absent in mice platelets which lack Syk, although phosphorylation of the Fc receptor gamma-chain is maintained. In contrast, tyrosine phosphorylation of platelet proteins by the G protein-coupled receptor agonist thrombin is maintained in mouse platelets deficient in Fc receptor gamma-chain or Syk. The absence of Fc receptor gamma-chain or Syk is accompanied by a loss of secretion and aggregation responses in collagen- but not thrombin-stimulated platelets. These observations provide the first direct evidence of an essential role for the immunoreceptor tyrosine-based activation motif (ITAM) in signalling by a non-immune receptor stimulus.

  • Keywords:

    • collagen,
    • Fc receptor gamma-chain,
    • ITAM,
    • platelets,
    • Syk