Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes

Susanna Fagerholm, Tiina J. Hilden, Carl G. Gahmberg

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)1670-1678
    Number of pages9
    JournalEuropean Journal of Immunology
    Volume32
    Issue number6
    DOIs
    Publication statusPublished - Jun 2002

    Cite this

    Fagerholm, Susanna ; Hilden, Tiina J. ; Gahmberg, Carl G. / Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes. In: European Journal of Immunology. 2002 ; Vol. 32, No. 6. pp. 1670-1678.
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    abstract = "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.",
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    Lck tyrosine kinase is important for activation of the CD11a/CD18-integrins in human T lymphocytes. / Fagerholm, Susanna; Hilden, Tiina J.; Gahmberg, Carl G.

    In: European Journal of Immunology, Vol. 32, No. 6, 06.2002, p. 1670-1678.

    Research output: Contribution to journalArticle

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    AU - Fagerholm, Susanna

    AU - Hilden, Tiina J.

    AU - Gahmberg, Carl G.

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    AB - 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.

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    JF - European Journal of Immunology

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