Interleukin-2 induces beta2-integrin-dependent signal transduction involving the focal adhesion kinase-related protein B (fakB)
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beta2 integrin molecules are involved in a multitude of cellular events, including adhesion, migration, and cellular activation. Here, we studied the influence of beta2 integrins on interleukin-2 (IL-2)-mediated signal transduction in human CD4(+) T cell lines obtained from healthy donors and a leukocyte adhesion deficiency (LAD) patient. We show that IL-2 induces tyrosine phosphorylation of a 125-kDa protein and homotypic adhesion in beta2 integrin (CD18)-positive but not in beta2-integrin-negative T cells. EDTA, an inhibitor of integrin adhesion, blocks IL-2-induced tyrosine phosphorylation of the 125-kDa protein but not other proteins in beta2-integrin-positive T cells. Likewise, a beta2 integrin (CD18) antibody selectively inhibits induction of the 125-kDa phosphotyrosine protein, whereas cytokine-mediated tyrosine phosphorylation of other proteins is largely unaffected. Immunoprecipitation experiments indicate that the IL-2-induced 125-kDa phosphotyrosine protein is the focal adhesion kinase-related protein B (fakB). Thus, IL-2 induces strong tyrosine phosphorylation of fakB in beta2-integrin-positive but not in beta2-integrin-negative T cells, and CD18 mAb selectively blocks IL-2-induced fakB-tyrosine phosphorylation in beta2-integrin-positive T cells. In parallel experiments, IL-2 does not induce or augment tyrosine phosphorylation of p125(FAK). In conclusion, our data indicate that IL-2 induces beta2-integrin-dependent signal transduction events involving the tyrosine kinase substrate fakB.
Original language | English |
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Journal | Proceedings of the National Academy of Science of the United States of America |
Volume | 95 |
Issue number | 12 |
Pages (from-to) | 6959-64 |
Number of pages | 5 |
ISSN | 0027-8424 |
Publication status | Published - 1998 |
Bibliographical note
Keywords: Antigens, CD18; CD4-Positive T-Lymphocytes; Cell Adhesion Molecules; Cell Line; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Humans; Phosphoproteins; Phosphorylation; Protein-Tyrosine Kinases; Signal Transduction
ID: 8545490