Phosphorylation of the LFA-1 integrin beta2-chain on Thr-758 leads to adhesion, Rac-1/Cdc42 activation, and stimulation of CD69 expression in human T cells

Susanna M. Nurmi, Matti Autero, Anna K. Raunio, Carl G. Gahmberg, Susanna C. Fagerholm

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    39 Citations (Scopus)

    Abstract

    Phosphorylation of the leukocyte function-associated antigen-1 (LFA-1) integrin ß2-chain on Thr-758 occurs after T cell receptor stimulation and leads to 14-3-3 recruitment to the integrin, actin cytoskeleton reorganization, and increased adhesion. Here, we have investigated the signaling effects of ß2 integrin Thr-758 phosphorylation. A penetratin-coupled phospho-Thr-758-ß2 peptide (mimicking the part of the integrin ß-chain surrounding Thr-758) stimulated adhesion of human T cells to the LFA-1 ligand intercellular adhesion molecule-1 (ICAM-1). Additionally, the peptide activated the small GTPases Rac-1 and Cdc42 in T cells. Constitutively active forms of Rac-1 and Cdc42, but not Rho, could compensate for the reduction of cell adhesion to ICAM-1 caused by the T758A mutation in the ß2 integrin. Additionally, the active GTPases salvaged the cell-spreading defect of T758A integrin-transfected cells on coated ICAM-1. A dominant negative form of Cdc42, on the other hand, significantly reduced wild-type ß2 integrin-mediated cell adhesion and spreading. In a T cell stimulation system, the pThr-758 penetratin peptide acted in a similar manner to coated ICAM-1 to increase T cell receptor-induced CD69 expression. These results show that Thr-758-phosphorylated LFA-1 is upstream of Rac-1/Cdc42, cell adhesion, and costimulatory activation of human T cells, thus identifying phosphorylation of Thr-758 in ß2 as a proximal element in LFA-1 signaling.© 2007 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)968-975
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume282
    Issue number2
    DOIs
    Publication statusPublished - Jan 2007

    Keywords

    • Actin cytoskeleton reorganization
    • Cell stimulation systems
    • Costimulatory activation
    • Cell adhesion
    • Cells
    • Computer simulation
    • Enzymes
    • Peptides
    • Phosphorylation
    • Antigens

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