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  • The EMBO Journal (2001) 20, 1232 - 1244
  • doi:10.1093/emboj/20.6.1232

A novel function for the Tec family tyrosine kinase Itk in activation of bold beta1 integrins by the T-cell receptor

Melody L. Woods1,2,3, Wendy J. Kivens1,2,3, Margaret A. Adelsman1,2,3, Yun Qiu1,3, Avery August4 and Yoji Shimizu1,2,3

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
  2. Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
  3. Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455, USA
  4. Immunology Research Laboratories, Department of Veterinary Science, The Pennsylvania State University, University Park, PA 16802, USA

Correspondence to:

Yoji Shimizu, E-mail: shimi002@tc.umn.edu

Received 29 September 2000; Accepted 18 January 2001; Revised 28 December 2000

Stimulation of T cells via the CD3–T-cell receptor (TCR) complex results in rapid increases in beta1 integrin-mediated adhesion via poorly defined intracellular signaling events. We demonstrate that TCR-mediated activation of beta1 integrins requires activation of the Tec family tyrosine kinase Itk and phosphatidylinositol 3-kinase (PI 3-K)-dependent recruitment of Itk to detergent-insoluble glycosphingolipid-enriched microdomains (DIGs) via binding of the pleckstrin homology domain of Itk to the PI 3-K product PI(3,4,5)-P3. Activation of PI 3-K and the src family kinase Lck, via stimulation of the CD4 co-receptor, can initiate beta1 integrin activation that is dependent on Itk function. Targeting of Itk specifically to DIGs, coupled with CD4 stimulation, can also activate beta1 integrin function independently of TCR stimulation. Changes in beta1 integrin function mediated by TCR activation of Itk are also accompanied by Itk-dependent modulation of the actin cytoskeleton. Thus, TCR-mediated activation of beta1 integrins involves membrane relocalization and activation of Itk via coordinate action of PI 3-K and a src family tyrosine kinase.

  • Keywords:

    • integrin,
    • Itk,
    • Lck,
    • phosphatidylinositol 3-kinase,
    • T lymphocyte