CD98 induces LFA‐1‐mediated cell adhesion in lymphoid cells via activation of Rap1

Abstract
CD98 is a multifunctional heterodimeric membrane protein involved in the regulation of cell adhesion as well as amino acid transport. We show that CD98 cross‐linking persistently activates Rap1 GTPase in a LFA‐1‐dependent manner and induces LFA‐1/ICAM‐1‐mediated cell adhesion in lymphocytes. Specific phosphatidylinositol‐3‐kinase (PI3K) inhibitors suppressed both LFA‐1 activation and Rap1GTP generation, and abrogation of Rap1GTP by retroviral over‐expression of a specific Rap1 GTPase activating protein, SPA‐1, totally inhibited the LFA‐1/ICAM‐1‐mediated cell adhesion. These results suggest that CD98 cross‐linking activates LFA‐1 via the PI3K signaling pathway and induces accumulation of Rap1GTP in a LFA‐1‐dependent manner, which in turn mediates the cytoskeleton‐dependent cell adhesion process.