title: Beta2-integrin, LFA-1, and TCR/CD3 synergistically induce tyrosine phosphorylation of focal adhesion kinase (pp125(FAK)) in PHA-activated T cells.
abstract: Complete T cell activation requires not only a first signal via TCR/CD3 engagement but also a costimulatory signal through accessory receptors such as CD2, CD28, or integrins. Focal adhesion kinase, pp125(FAK) (FAK), was previously shown to be localized in focal adhesions in fibroblasts and to be involved in integrin-mediated cellular activation. Although signaling through beta1- or beta3-integrins induces tyrosine phosphorylation of FAK, there has been no evidence that activation of T cells through the beta2-integrin, LFA-1, involves FAK. We report here that crosslinking of LFA-1 induces tyrosine phosphorylation of FAK in PHA-activated T cells. Moreover, cocrosslinking with anti-LFA-1 mAb and suboptimal concentration of anti-CD3 mAb markedly increases tyrosine phosphorylation of FAK in an antibody-concentration-dependent and time-kinetics-dependent manner compared with stimulation through CD3 alone, which correlates well with enhanced proliferation of PHA-activated T cells. Furthermore, LFA-1beta costimulation with CD3 induces tyrosine phosphorylation of Syk associated with FAK. These results indicate, for the first time, 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 Medicine, Osaka Dental University, Hirakata, Osaka, 573, Japan.
authors.forename: F H
authors.initials: FH
authors.lastname: Tabassam
authors.forename: H
authors.initials: H
authors.lastname: Umehara
authors.forename: J Y
authors.initials: JY
authors.lastname: Huang
authors.forename: S
authors.initials: S
authors.lastname: Gouda
authors.forename: T
authors.initials: T
authors.lastname: Kono
authors.forename: T
authors.initials: T
authors.lastname: Okazaki
authors.forename: J M
authors.initials: JM
authors.lastname: van Seventer
authors.forename: N
authors.initials: N
authors.lastname: Domae
mesh_terms: D018821:CD18 Antigens / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D010766:Phosphorylation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020239:Receptor Cross-Talk; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D018821:CD18 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D010835:Phytohemagglutinins; D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human