Pervanadate-induced adhesion of CD4+ T cell to fibronectin is associated with tyrosine phosphorylation of paxillin.
The initial stages of T cell activation involve tyrosine protein kinase-mediated intracellular signaling events. Integrin-mediated adhesion of CD4+ T lymphocytes to extracellular matrix glycoproteins, such as fibronectin, is an activation-dependent process. The involvement of tyrosine protein kinases in the adhesion of CD4+ T cells to fibronectin was examined using pervanadate, a protein-tyrosine phosphatase inhibitor. Pervanadate induced the adhesion of human CD4+ T cells to immobilized fibronectin in a beta1 integrin-mediated fashion, and adhesion was associated with an increase of protein tyrosine phosphorylation. Tyrosine protein kinase inhibitors abrogated both T cell adhesion and intracellular protein tyrosine phosphorylation. Participation of cytoskeletal proteins in the pervanadate-induced T cell adhesion was indicated because cytoskeleton disruption by cytochalasin B inhibited cell adhesion to fibronectin. We demonstrate that the cytoskeletal protein paxillin underwent time-dependent tyrosine phosphorylation simultaneously with pervanadate-induced T cell adhesion to fibronectin. Tyrosine phosphorylation of paxillin was related to cell adhesion, since pretreatment of T cells with cytochalasin B abrogated both adhesion and phosphorylation. This study demonstrates a correlation between activation of protein tyrosine kinases, tyrosine phosphorylation of paxillin, and integrin-mediated T cell adhesion to extracellular matrix glycoproteins.
Miron
S
S
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Kachalsky
S G
SG
Hershkoviz
R
R
Lider
O
O
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014638:Vanadates / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; C076715:pervanadate; D019000:Phosphotyrosine; D003571:Cytochalasin B; D014638:Vanadates; D011505:Protein-Tyrosine Kinases; D013755:Tetradecanoylphorbol Acetate