Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes.
CD11a/CD18 (beta2)-integrins are expressed on leukocytes and are involved in cell adhesion and signaling. Despite extensive studies the signaling pathways and molecular mechanisms involved in integrin regulation in T cells remain not completely understood. We have now studied the involvement of the tyrosine kinase Lck in the regulation of CD11a/CD18 function in Jurkat T cells. Using the Src-family kinase inhibitor PP2, we found that CD3 ligation-induced adhesion to ICAM-1 was inhibited by PP2 at the same concentration required for complete inhibition of the MAP kinase pathway, implicating a role for Lck in integrin activation. We therefore used the Lck-deficient Jurkat cell line JCaM1.6 to further examine the involvement of Lck in integrin regulation. Interestingly, JCaM1.6 cells showed dramatically reduced levels of both CD3- and phorbol ester-induced adhesion to coated ICAM-1 as compared to normal Jurkat cells. By using flow cytometry and cell surface labeling, it was found that the surface expression of the CD11a/CD18-integrins was significantly lower in Lck-deficient T cells as compared to normal Jurkat cells. CD18 was expressed as a mature and an immaturely glycosylated form in Jurkat T cell lines, and predominantly the immature form, not associated with CD11a, was found in Lck-deficient cells. Retransfection of human Lck in JCaM1.6 cells restored adhesion. Thus, Lck is involved in regulating CD11a/CD18-integrins in T cells.
Fagerholm
Susanna
S
Department of Biosciences, Division of Biochemistry, University of Helsinki, Helsinki, Finland.
Hilden
Tiina J
TJ
Gahmberg
Carl G
CG
D018821:CD18 Antigens / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D002449:Cell Aggregation; D019281:Dimerization; D006031:Glycosylation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000502:physiology*
D018821:CD18 Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D015240:Phorbol 12,13-Dibutyrate; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)