Rap1B and Rap2B translocation to the cytoskeleton by von Willebrand factorinvolves Fc gamma II receptor-mediated protein tyrosine phosphorylation

Citation
M. Torti et al., Rap1B and Rap2B translocation to the cytoskeleton by von Willebrand factorinvolves Fc gamma II receptor-mediated protein tyrosine phosphorylation, J BIOL CHEM, 274(19), 1999, pp. 13690-13697
Citations number
29
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
19
Year of publication
1999
Pages
13690 - 13697
Database
ISI
SICI code
0021-9258(19990507)274:19<13690:RARTTT>2.0.ZU;2-K
Abstract
Stimulation of human platelets with von Willebrand factor (vWF) induced the translocation of the small GTPases Rap1B and Rap2B to the cytoskeleton. Th is effect was specifically prevented by an anti-glycoprotein Ib monoclonal antibody or by the omission of stirring, but was not affected by the peptid e RGDS, which antagonizes binding of adhesive proteins to platelet integrin s. Association of Rap2B with the cytoskeleton was very rapid, while translo cation of Rap1B occurred in a later phase of platelet activation and was to tally inhibited by cytochalasin D. vWF also induced the rapid tyrosine phos phorylation of several proteins that was prevented by the tyrosine kinases inhibitor genistein and by cAMP-increasing agents. Under these conditions, also the association of Rap1B and Rap2B with the cytoskeleton was prevented . Translocation of Rap proteins to the cytoskeleton induced by vWF, but not by thrombin, was inhibited by a monoclonal antibody against the Fc gamma I I receptor. The same antibody inhibited vWF-induced tyrosine phosphorylatio n of selected substrates with molecular masses of about 75, 95, and 150 kDa . Three of these substrates were identified as the tyrosine kinase pp72(syk ), the phospholipase C gamma 2, and the inositol 5-phosphatase SHIP. Our re sults indicate that translocation of Rap1B and Rap2B to the cytoskeleton is regulated by tyrosine kinases and suggest a novel role for the Fc gamma II receptor in the mechanism of platelet activation by vWF.