Involvement of a protein kinase C and protein phosphatases in adhesion of CD4+ T cells to and detachment from extracellular matrix proteins.
For immune surveillance and function to be effective, T lymphocytes constantly recirculate via lymph and blood between lymphoid organs and body tissues. To enable efficient cell movement and migration, cell adhesion to components of the basement membrane and the extracellular matrix (ECM) must be a rapid and transitory process. Whether phosphorylation and dephosphorylation of cellular proteins are involved in this phenomena was explored by monitoring the adhesion of T cells to immobilized ECM proteins. A short exposure of 51Cr-labeled human CD4+ T cells to phorbol esters in vitro induced a rapid beta 1-integrin-mediated adhesion to both fibronectin and laminin, as determined by inhibition with anti-integrin antibodies. Adhesion was reversible; detachment from the immobilized ECM ligands occurred between 20 and 120 min without further intervention. This T cell adhesion was regulated by the activation of protein kinase C because (a) staurosporine and H-7 inhibitors of protein kinase C suppressed T cell adhesion, and (b) PMA-induced down-regulation of intracellular levels of protein kinase C was associated with the abrogation of the T cell adhesiveness to fibronectin and laminin. Furthermore, inhibition of protein phosphatases activity by okadaic acid delayed the detachment of the T cells from fibronectin or laminin. Thus, we suggest that T cell-ECM interactions such as adhesion and detachment are regulated, respectively, by protein kinase C and protein phosphatases.
Miron
S
S
Department of Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Tirosh
I
I
Schechter
Y
Y
Yayun
A
A
Lider
O
O
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000470:Alkaloids / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement; D004988:Ethers, Cyclic / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism*; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D019311:Staurosporine; D013601:T-Lymphocytes / Q000378:metabolism*
D000470:Alkaloids; D015704:CD4 Antigens; D004988:Ethers, Cyclic; D005353:Fibronectins; D016023:Integrins; D007546:Isoquinolines; D007797:Laminin; D010879:Piperazines; D019319:Okadaic Acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D019311:Staurosporine