A ROLE FOR BRUTONS TYROSINE KINASE (BTK) IN PLATELET ACTIVATION BY COLLAGEN

Bruton's tyrosine kinase (Btk) is essential for normal B-cell receptor signalling. The lack of expression of functional Btk in humans leads to the B-cell deficiency X-linked agammaglobulinaemia (XLA), We report here that Btk is also important for signalling via the collagen recep tor glycoprotein VI (GPVI) in platelets. GPVI is coupled to the Fc rec eptor gamma chain (FcR gamma. The FcR gamma-chain contains a consensus sequence known as the immune-receptor tyrosine-based activation motif (ITAM). Tyrosine phosphorylation of the ITAM upon GPVI stimulation is the initial step in the regulation of phospholipase C gamma 2 (PLC ga mma 2) isoforms via the tyrosine kinase p72(Syk)(Syk) in platelets. He re we show that collagen and a collagen related peptide (CRP), which b inds to GPVI but does not bind to the integrin alpha(2)beta(1), induce d Btk tyrosine phosphorylation in platelets. Aggregation, dense granul e secretion and calcium mobilisation were significantly diminished but not completely abolished in platelets from XLA patients in response t o collagen and CRP. These effects were associated with a reduction in tyrosine phosphorylation of PLC gamma 2. In contrast, aggregation and secretion stimulated by thrombin in Btk-deficient platelets were not s ignificantly altered. Our results demonstrate that Btk is important fo r collagen signalling via GPVI, but is not essential for thrombin-medi ated platelet activation. (C) Current Biology Ltd ISSN 0960-9822.