T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells
2010 (English)In: PloS one, ISSN 1932-6203, Vol. 5, no 3, e9761- p.Article in journal (Refereed) Published
BACKGROUND: The chemokine CXCL12/SDF-1alpha 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 beta subunit. However, the molecular mechanisms for how TSAd influences cellular migration have not been characterized in detail. PRINCIPAL FINDINGS: We 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. CONCLUSION: We 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.
Place, publisher, year, edition, pages
2010. Vol. 5, no 3, e9761- p.
Cell and Molecular Biology Medical Genetics
IdentifiersURN: urn:nbn:se:uu:diva-123739DOI: 10.1371/journal.pone.0009761ISI: 000276456300009PubMedID: 20305788OAI: oai:DiVA.org:uu-123739DiVA: diva2:315568