Phosphoinositide 3-kinase and integrin signalling are involved in activation of Bruton tyrosine kinase in thrombin-stimulated platelets

Bruton tyrosine kinase (Btk) plays a crucial role in the differentiation of B lymphocytes and belongs to the group of Tec kinases, which are character ised by the presence of a pleckstrin homology domain. Here we show that Btk is activated and undergoes tyrosine phosphorylation upon challenge of plat elet thrombin receptor, these responses requiring engagement of alpha(IIb)/ beta(3) integrin and phosphoinositide 3-kinase activity. These data unravel a novel signalling pathway involving Btk downstream of an adhesive recepto r via a complex regulation implicating the products of phosphoinositide 3-k inase, which might act to anchor Btk at the membrane. (C) 1999 Federation o f European Biochemical Societies.