Effects of integrin alpha IIb(R995A) mutation on receptor affinity and pp125 (FAK) phosphorylation / 中国医学科学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of cytoplasmic domain of integrin alpha IIb in platelet signal transduction.</p><p><b>METHODS</b>Binding capacity of integrin alpha IIb(R995A) to antibody platelet activation complex-1 (PAC-1) and pp125 focal adhesion kinase (FAK) phosphorylation of cells were detected by flow cytometry, immune precipitation, and Western blotting.</p><p><b>RESULTS</b>Without activation, wild-type alpha IIb beta3 Chinese hamster ovary (CHO) cells failed to bind to PAC-1, but mutant chimera alpha IIb(R995A)beta3 CHO cells were able to bind with PAC-1. Furthermore, phosphorylation of pp125 (FAK) in wild-type alpha IIb beta3 CHO cells occured only when cells were adhered to fibrinogen, but could not be detected in bovine serum albumin suspension. However in the mutant chimera group, it could be detected in both conditions.</p><p><b>CONCLUSION</b>The mutation in integrin alpha IIb(R995A) alters its affinity state as a receptor, thus also mediating cytoplasmic signal transduction leading to the phosphorylation of pp125 (FAK) without ligand binding.</p>