CD7-Mediated Regulation of Integrin Adhesiveness on Human T Cells Involves Tyrosine Phosphorylation-Dependent Activation of Phosphatidylinositol 3-Kinase

Anissa S H Chan, James L. Mobley, Gregg B. Fields, Yoji Shimizu

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

The functional activity of integrin receptors on T cells is dynamically regulated so that T cells can alternate rapidly between adhesive and nonadhesive states. The CD7 Ag is one of several molecules on T cells that can transduce intracellular signals that rapidly up-regulate integrin-mediated adhesion. We demonstrate in this report that the signaling pathway that CD7 utilizes to regulate integrin activity involves the lipid kinase phosphatidylinositol 3-kinase (PI 3-K). CD7 stimulation of both Jurkat T cells and resting human peripheral blood CD4 + T cells results in rapid association and activation of PI 3-K with CD7. Phosphopeptide competition assays demonstrate that the association of CD7 with PI 3-K is dependent on tyrosine phosphorylation of the SH2 binding motif Tyr-Glu-Asp-Met (YEDM) in the CD7 cytoplasmic domain. A role for PI 3-K in the regulation of integrin function by CD7 is demonstrated by: 1) the ability of two structurally distinct PI 3-K inhibitors, wortmannin and LY294002, to inhibit CD7-mediated increases in β 1 integrin function of human T cells; and 2) inhibition of CD7-mediated activation of β 1 integrin function in human T cells by expression of a dominant negative form of the p85 subunit of PI 3-K. These results demonstrate that the CD7 Ag on human T cells is coupled to PI 3-K and that this association is relevant to CD7-mediated signaling events, specifically CD7-induced increases in integrin adhesiveness. Furthermore, these studies provide important new evidence implicating PI 3-K in the regulation of integrin adhesiveness by multiple cell surface signaling receptors.

Original languageEnglish (US)
Pages (from-to)934-942
Number of pages9
JournalJournal of Immunology
Volume159
Issue number2
StatePublished - Jul 15 1997

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