T Cell Specific Adapter Protein (TSAd) Interacts with Tec Kinase ITK to Promote CXCL12 Induced Migration of Human and Murine T Cells |
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| Authors: | Tone Berge Vibeke Sundvold-Gjerstad Stine Granum Thorny C B Andersen Gunn B Holthe Lena Claesson-Welsh Amy H Andreotti Marit Inngjerdingen Anne Spurkland |
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| Institution: | 1. Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.; 2. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.; 3. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa, United States of America.;University Paris Sud, France |
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| Abstract: | BackgroundThe chemokine CXCL12/SDF-1α interacts with its G-protein coupled receptor CXCR4 to induce migration of lymphoid and endothelial cells. T cell specific adapter protein (TSAd) has been found to promote migration of Jurkat T cells through interaction with the G protein β subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail.Principal FindingsWe show that TSAd is required for tyrosine phosphorylation of the Lck substrate IL2-inducible T cell kinase (Itk). Presence of Itk Y511 was necessary to boost TSAd''s effect on CXCL12 induced migration of Jurkat T cells. In addition, TSAd''s ability to promote CXCL12-induced actin polymerization and migration of Jurkat T lymphocytes was dependent on the Itk-interaction site in the proline-rich region of TSAd. Furthermore, TSAd-deficient murine thymocytes failed to respond to CXCL12 with increased Itk phosphorylation, and displayed reduced actin polymerization and cell migration responses.ConclusionWe propose that TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements. |
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