title: Beta 2-integrin, LFA-1-mediated p125FAK activation.
abstract: Accumulation of T cells at inflammatory sites is one of the characteristic features of infection, autoimmune and chronic inflammatory diseases. Optimal activation of T cells requires the binding of the MHC/Ag complex with T cell receptor, as well as a secondary signal initiated by costimulatory molecules such as CD2, CD28 or integrins. Focal adhesion kinase, pp125FAK (FAK) has been previously shown to be localized in focal adhesions in fibroblasts and to be involved in integrin-mediated cellular activation. Although signaling through beta 1- or beta 3-integrins induces tyrosine phosphorylation of FAK, there has been no evidence that activation of T cells through the beta 2-integrin, lymphocyte function-associated antigen (LFA)-1, involves FAK. We report here that crosslinking of LFA-1 induces tyrosine phosphorylation of FAK in PHA-activated T cells. Moreover, co-crosslinking with anti-LFA-1 monoclonal antibody (mAb) and suboptimal concentration of anti-CD3 mAb markedly increases tyrosine phosphorylation of FAK in an antibody-concentration and time-dependent manner compared with stimulation through CD3 alone. Furthermore this increased phosphorylation correlates well with the enhanced proliferation of PHA-activated T cells. Results indicate that signals mediated by LFA-1 can regulate FAK, suggesting that LFA-1-mediated T cell costimulation may be involved in T cell activation at least partially through FAK.
authors.affiliation: Department of Internal Medicine, Osaka Dental University.
authors.forename: F H
authors.initials: FH
authors.lastname: Tabassam
authors.forename: H
authors.initials: H
authors.lastname: Umehara
authors.forename: N
authors.initials: N
authors.lastname: Domae
mesh_terms: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D015151:Immunoblotting; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D016169:Lymphocyte Function-Associated Antigen-1; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human