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Thromb Haemost 2001; 85(02): 331-340
DOI: 10.1055/s-0037-1615689
Review Article
Schattauer GmbH

Genetic and Pharmacological Analyses of Involvement of Src-family, Syk and Btk Tyrosine Kinases in Platelet Shape Change

Src-kinases Mediate Integrin αIIb β3 Inside-out Signaling during Shape Change
Markus Bauer
1   Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität München, München, Germany
,
Petra Maschberger
1   Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität München, München, Germany
,
Lynn Quek
2   Dr. von Haunersches Kinderspital, Klinikum der Universität München, München, Germany;
,
Stephen J. Briddon
2   Dr. von Haunersches Kinderspital, Klinikum der Universität München, München, Germany;
,
Debabrata Dash   *
1   Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität München, München, Germany
,
Michael Weiss
3   Department of Pharmacology, Oxford University, Oxford, England
,
Steve P. Watson
2   Dr. von Haunersches Kinderspital, Klinikum der Universität München, München, Germany;
,
Wolfgang Siess
1   Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum der Universität München, München, Germany
› Author Affiliations
Further Information

Publication History

Received 16 April 2000

Accepted after resubmission 25 August 2000

Publication Date:
08 December 2017 (online)

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Summary

Platelet shape change was found to be associated with an increase in protein tyrosine phosphorylation upon stimulation of thrombin-, ADPand thromboxane A2-G-protein coupled receptors in human platelets and thromboxane A2 receptors in mouse platelets. By using PP1 and PD173956, two structurally unrelated specific inhibitors of Src-family tyrosine kinases, and mouse platelets deficient in the Src-kinase Fyn or Lyn, we show that Src-family kinases cause the increase in protein tyrosine phosphorylation. We further detected that the non-Src tyrosine kinase Syk was activated during shape change in a manner dependent on Src-family kinaseactivation. The pharmacological experiments and the studies on Fyn-, Lyn- and Syk-deficient mouse platelets showed that neither Src-family kinases nor Syk are functionally involved in shape change. Also human platelets deficient of the tyrosine kinase Btk showed a normal shape change. Binding of PAC-1 that recognizes activated integrin αIIb β3 complexes on the platelet surface was enhanced during shape change and blocked by inhibition of Src-kinases. We conclude that the activation of Src-kinases and the subsequent Syk stimulation upon activation of G-protein coupled receptors are not involved in the cytoskeletal changes underlying shape change of human and mouse platelets, but that the stimulation of this evolutionary conserved pathway leads to integrin αIIb β3 exposure during shape change.

Keywords

Platelet - shape change - integrin αIIb β3 - tyrosine phosphorylation - Src - Syk - Btk - heterotimbric G-protein - ADP - thrombin - thromboxane

* Present address: Banaras Hindu University, Institute of Medical Sciences, Department of Biochemistry, Varanasi 221005, India


 

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