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

FEBS Letters

Minato, Nagahiro²  Kinashi, Tatsuo³  Harazaki, Masashi²  Suga, Koji²  Katagiri, Koko³  Hattori, Masakazu²  Iizuka, Tadahiko¹ 

[1] Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan;Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan;Bayer Chair-Department of Molecular Immunology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

关键词: CD98;    LFA-1;    Rap1;    Phosphatidylinositol-3-kinase;    Cell adhesion;    moAb;    monoclonal antibody;    PI3K;    phosphatidylinositol-3-kinase;    ERK;    external signal-regulated kinase;    NHIg;    normal hamster IgG;    APC;    antigen-presenting cells;   

DOI  :  10.1016/S0014-5793(00)02222-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown