T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells.

T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells.

<h4>Background</h4>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 protei...

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Main 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-03-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009761&type=printable
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Summary:<h4>Background</h4>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.<h4>Principal findings</h4>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.<h4>Conclusion</h4>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.
ISSN:1932-6203

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