Regulation of CXC chemokine receptor 4-mediated migration by the Tec family tyrosine kinase ITK

Angela M. Fischer, Jason C. Mercer, Archana Iyer, Melanie J. Ragin, Avery August

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Chemokines are critical in controlling lymphocyte traffic and migration. The CXC chemokine CXCL12/SDF-1α 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-1α stimulation, and this requires Src and phosphatidylinositol 3-kinase activities. ITK regulates the ability of CXCL12/SDF-1α 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-1α. 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-1α-mediated actin polymerization. Our data suggest that ITK may regulate the ability of CXCR4 to induce T cell migration.

Original languageEnglish (US)
Pages (from-to)29816-29820
Number of pages5
JournalJournal of Biological Chemistry
Volume279
Issue number28
DOIs
StatePublished - Jul 9 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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