Regulation and function of WASp in platelets by the collagen receptor, glycoprotein VI.

摘要: Wiskott Aldrich syndrome (WAS) is an X-linked recessive disorder associated with abnormalities in platelets and lymphocytes giving rise to thrombocytopenia immunodeficiency. WAS caused by a mutation the gene encoding cytoskeletal protein (WASp). Despite its importance, role of WASp platelet function not established. was recently shown undergo tyrosine phosphorylation after activation collagen, suggesting that it may play selective adhesion molecule. In present study, we show heavily phosphorylated collagen-related peptide (CRP) binds collagen receptor glycoprotein (GP) VI, but integrin alpha2beta1. Tyrosine blocked Src family kinase inhibitors reduced treatment wortmannin patients agammaglobulinemia (XLA), condition lack functional expression Btk. This indicates kinases, phosphatidylinositol 3-kinase (PI 3-kinase), Btk all contribute regulation WASp. The importance investigated 2 brothers who no detectable Platelet aggregation secretion from dense granules induced CRP thrombin slightly enhanced relative controls. Furthermore, there apparent difference morphology stimulation these agonists. These observations suggest does critical intracellular signaling downstream kinase-linked G protein-coupled receptors platelets.