First Author | Fischer AM | Year | 2004 |
Journal | J Biol Chem | Volume | 279 |
Issue | 28 | Pages | 29816-20 |
PubMed ID | 15123627 | Mgi Jnum | J:91612 |
Mgi Id | MGI:3047528 | Doi | 10.1074/jbc.M312848200 |
Citation | Fischer AM, et al. (2004) Regulation of CXC chemokine receptor 4-mediated migration by the Tec family tyrosine kinase ITK. J Biol Chem 279(28):29816-20 |
abstractText | Chemokines are critical in controlling lymphocyte traffic and migration. The CXC chemokine CXCL12/SDF-1alpha interacts with its receptor CXCR4 to induce the migration of a number of different cell types. Although an understanding of the physiological functions of this chemokine is emerging, the mechanism by which it regulates T cell migration is still unclear. We show here that the Tec family kinase ITK is activated rapidly following CXCL12/SDF-1alpha stimulation, and this requires Src and phosphatidylinositol 3-kinase activities. ITK regulates the ability of CXCL12/SDF-1alpha to induce T cell migration as overexpression of wild-type ITK-enhanced migration, and T cells lacking ITK exhibit reduced migration as well as adhesion in response to CXCL12/SDF-1alpha. Further analysis suggests that ITK may regulate CXCR4-mediated migration and adhesion by altering the actin cytoskeleton, as ITK null T cells were significantly defective in CXCL12/SDF-1a-mediated actin polymerization. Our data suggest that ITK may regulate the ability of CXCR4 to induce T cell migration. |