TITLE

A novel function for the Tec family tyrosine kinase Itk in activation of ß1 integrins by the T-cell receptor

AUTHOR(S)
Woods, Melody L.; Kivens, Wendy J.; Adelsman, Margaret A.; Yun Qiu; August, Avery; Shimizu, Yoji
PUB. DATE
March 2001
SOURCE
EMBO Journal;3/15/2001, Vol. 20 Issue 6, p1232
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Stimulation of T cells via the CD3-T-cell receptor (TCR) complex results in rapid increases in ß1 integrin-mediated adhesion via poorly defined intracellular signaling events. We demonstrate that TCR-mediated activation of ß1 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 ß1 integrin activation that is dependent on Itk function. Targeting of Itk specifically to DIGs, coupled with CD4 stimulation, can also activate ß1 integrin function independently of TCR stimulation. Changes in ß1 integrin function mediated by TCR activation of Itk are also accompanied by Itk-dependent modulation of the actin cytoskeleton. Thus, TCR-mediated activation of ß1 integrins involves membrane relocalization and activation of Itk via coordinate action of PI 3-K and a src family tyrosine kinase.
ACCESSION #
12954982

 

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