Regulation of fibronectin and laminin binding activity in cultured human lymphoblastic cell lines.
The current study shows that a clonal derivative of the Jurkat cell line up-regulates both the avidity and density of the alpha 6/beta 1 receptor in response to phorbol 12-myristate 13-acetate (PMA). This derivative attaches to fibronectin and, to a lesser degree, laminin constitutively. Adhesion and spreading are dramatically up-regulated following treatment with PMA. The response on fibronectin peaks within 4 hours, is insensitive to cyclohexamide, can be blocked by monoclonal antibodies (Mabs) to the beta 1 and alpha 5 subunits of the beta 1 family of integrins, and is not associated with increased expression of the alpha 5 or beta 1 epitopes at the cell surface. In contrast, the response on laminin is biphasic. The early phase parallels the response on fibronectin. The second phase peaks after 48-72 hours of treatment with PMA, is sensitive to cycloheximide, can be blocked by Mabs to the beta 1 and alpha 6 subunits, and is associated with increased expression of the alpha 6 epitope. Both the density independent and dependent responses to PMA in Jurkat cells are blocked by the protein kinase inhibitor staurosporine. The HSB-2, CEM, Molt-4, and HPB-ALL T-lymphoblastic cell lines also up-regulate attachment to fibronectin and laminin following treatment with PMA. All four lines constitutively attach to fibronectin and show rapid up-regulation of attachment following treatment with PMA. None of the lines attach to laminin prior to PMA treatment; however, specific adhesion developed after 4-120 hours of treatment. The most mature lines (Jurkat and HPB-ALL) up-regulated adhesion on laminin more rapidly than the less phenotypically mature lines (CEM, Molt-4, and HSB-2). In summary, clonal derivatives of the Jurkat cell line up-regulated attachment to laminin through protein kinase dependent increases in alpha 6/beta 1 receptor avidity and density. In addition, the expression of functional receptors for laminin is linked to developmental maturity in a series of T-lymphoblastic cell lines.
Stoolman
L M
LM
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Wang
T L
TL
Situ
R
R
Varani
J
J
D000470:Alkaloids / Q000494:pharmacology; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism*; D019311:Staurosporine; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000470:Alkaloids; D005353:Fibronectins; D007797:Laminin; D017469:Receptors, Fibronectin; D017474:Receptors, Laminin; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate