A novel function for the Tec family tyrosine kinase Itk in activation of β1 integrins by the T-cell receptor

Melody L. Woods, Wendy J. Kivens, Margaret A. Adelsman, Yun Qiu, Avery August, Yoji Shimizu

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Stimulation of T cells via the CD3-T-cell receptor (TCR) complex results in rapid increases in β1 integrin-mediated adhesion via poorly defined intracellular signaling events. We demonstrate that TCR-mediated activation of β1 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 β1 integrin activation that is dependent on Itk function. Targeting of Itk specifically to DIGs, coupled with CD4 stimulation, can also activate β1 integrin function independently of TCR stimulation. Changes in β1 integrin function mediated by TCR activation of Itk are also accompanied by Itk-dependent modulation of the actin cytoskeleton. Thus, TCR-mediated activation of β1 integrins involves membrane relocalization and activation of Itk via coordinate action of PI 3-K and a src family tyrosine kinase.

Original languageEnglish (US)
Pages (from-to)1232-1244
Number of pages13
JournalEMBO Journal
Volume20
Issue number6
DOIs
StatePublished - Mar 15 2001

Fingerprint

T-Cell Antigen Receptor
Integrins
Phosphatidylinositol 3-Kinase
Protein-Tyrosine Kinases
Chemical activation
src-Family Kinases
Glycosphingolipids
CD4 Antigens
T-cells
Actin Cytoskeleton
Detergents
Tec protein-tyrosine kinase
Actins
Adhesion
T-Lymphocytes
Modulation
Membranes

Keywords

  • Integrin
  • Itk
  • Lck
  • Phosphatidylinositol 3-kinase
  • T lymphocyte

Cite this

A novel function for the Tec family tyrosine kinase Itk in activation of β1 integrins by the T-cell receptor. / Woods, Melody L.; Kivens, Wendy J.; Adelsman, Margaret A.; Qiu, Yun; August, Avery; Shimizu, Yoji.

In: EMBO Journal, Vol. 20, No. 6, 15.03.2001, p. 1232-1244.

Research output: Contribution to journalArticle

Woods, Melody L. ; Kivens, Wendy J. ; Adelsman, Margaret A. ; Qiu, Yun ; August, Avery ; Shimizu, Yoji. / A novel function for the Tec family tyrosine kinase Itk in activation of β1 integrins by the T-cell receptor. In: EMBO Journal. 2001 ; Vol. 20, No. 6. pp. 1232-1244.
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