Document Detail


Regulation of CXC chemokine receptor 4-mediated migration by the Tec family tyrosine kinase ITK.
MedLine Citation:
PMID:  15123627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Angela M Fischer; Jason C Mercer; Archana Iyer; Melanie J Ragin; Avery August
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-04-26
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-05     Completed Date:  2004-08-24     Revised Date:  2012-06-01    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  29816-20     Citation Subset:  IM    
Affiliation:
Department of Veterinary Science, Pathobiology Graduate Program, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Movement / physiology*
Chemokine CXCL12
Chemokines, CXC / metabolism
Enzyme Activation
Humans
Jurkat Cells / metabolism*
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases / metabolism
Protein-Tyrosine Kinases / genetics,  metabolism*
Receptors, CXCR4 / metabolism*
Signal Transduction / physiology
src-Family Kinases / metabolism
Grant Support
ID/Acronym/Agency:
R01-AI51626/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/CXCL12 protein, human; 0/Chemokine CXCL12; 0/Chemokines, CXC; 0/Cxcl12 protein, mouse; 0/Receptors, CXCR4; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/emt protein-tyrosine kinase; EC 2.7.10.2/src-Family Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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