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

被引:80
作者
Woods, ML
Kivens, WJ
Adelsman, MA
Qiu, Y
August, A
Shimizu, Y [1 ]
机构
[1] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Sch Med, Ctr Immunol, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Sch Med, Ctr Canc, Minneapolis, MN 55455 USA
[4] Penn State Univ, Dept Vet Sci, Immunol Res Labs, University Pk, PA 16802 USA
关键词
integrin; Itk; Lck; phosphatidylinositol; 3-kinase; T lymphocyte;
D O I
10.1093/emboj/20.6.1232
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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)-P-3. 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.
引用
收藏
页码:1232 / 1244
页数:13
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