CD98 induces LFA-1-mediated cell adhesion in lymphoid cells via activation of Rap1.
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.
Suga
K
K
Department of Immunology and Cell Biology, Graduate School of Medicine, Kyoto University, Japan.
Katagiri
K
K
Kinashi
T
T
Harazaki
M
M
Iizuka
T
T
Hattori
M
M
Minato
N
N
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027261:Fusion Regulatory Protein-1; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism*
D000730:Androstadienes; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D027261:Fusion Regulatory Protein-1; D016169:Lymphocyte Function-Associated Antigen-1; D000081082:Phosphoinositide-3 Kinase Inhibitors; D018799:Intercellular Adhesion Molecule-1; D020827:rap1 GTP-Binding Proteins; D000077191:Wortmannin