HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Epler, J. A. Articles by Shimizu, Y. Search for Related Content PubMed PubMed Citation Articles by Epler, J. A. Articles by Shimizu, Y. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-PHENYLALANINE L-TYROSINE

Regulation of ß₁ Integrin-Mediated Adhesion by T Cell Receptor Signaling Involves ZAP-70 but Differs from Signaling Events That Regulate Transcriptional Activity¹

Department of Laboratory Medicine and Pathology, Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, MN 55455

Stimulation of the CD3/TCR results within minutes in an increase in T cell adhesion mediated by ß₁ integrins. The biochemical pathways that control CD3-mediated increases in ß₁ integrin-mediated adhesion remain poorly characterized. In this study, the role of the tyrosine kinase ZAP-70 in the regulation of ß₁ integrin activity by the CD3/TCR was investigated. CD3 stimulation did not increase ß₁ integrin-mediated adhesion of the ZAP-70-deficient Jurkat T cell line, P116, to the ß₁ integrin ligand fibronectin. Reintroduction of wild-type ZAP-70, but not a kinase-inactive variant, K369R, corrected the adhesive defect observed in P116 T cells. In addition, the kinase-inactive ZAP-70 mutant inhibited CD3-induced adhesion of primary human T cell blasts. Interestingly, a ZAP-70 mutant with a tyrosine to phenylalanine substitution at position 319 (Y319F) restored the adhesive defect in P116 T cells, even though Y319F ZAP-70 failed to fully reconstitute CD3-initiated NF-AT-dependent transcription and tyrosine phosphorylation of the LAT adapter protein. Finally, expression of mutants of LAT and the SLP-76 adapter protein that modulate CD3-mediated activation of an NF-AT reporter gene failed to block CD3-induced increases in ß₁ integrin-mediated adhesion. These observations support a model in which the tyrosine kinase activity of ZAP-70 kinase is critical for regulation of ß₁ integrin activity by CD3/TCR. However, the signaling events downstream of ZAP-70 that regulate CD3/TCR-mediated activation of ß₁ integrin function exhibit key differences when compared with the signaling pathways that regulate transcriptional events initiated by CD3/TCR stimulation.

This article has been cited by other articles:

				J. Horn, X. Wang, P. Reichardt, T. E. Stradal, N. Warnecke, L. Simeoni, M. Gunzer, D. Yablonski, B. Schraven, and S. Kliche Src Homology 2-Domain Containing Leukocyte-Specific Phosphoprotein of 76 kDa Is Mandatory for TCR-Mediated Inside-Out Signaling, but Dispensable for CXCR4-Mediated LFA-1 Activation, Adhesion, and Migration of T Cells J. Immunol., November 1, 2009; 183(9): 5756 - 5767. [Abstract] [Full Text] [PDF]

				J. C. Nolz, R. B. Medeiros, J. S. Mitchell, P. Zhu, B. D. Freedman, Y. Shimizu, and D. D. Billadeau WAVE2 Regulates High-Affinity Integrin Binding by Recruiting Vinculin and Talin to the Immunological Synapse Mol. Cell. Biol., September 1, 2007; 27(17): 5986 - 6000. [Abstract] [Full Text] [PDF]

				S. Goda, A. C. Quale, M. L. Woods, A. Felthauser, and Y. Shimizu Control of TCR-Mediated Activation of {beta}1 Integrins by the ZAP-70 Tyrosine Kinase Interdomain B Region and the Linker for Activation of T Cells Adapter Protein J. Immunol., May 1, 2004; 172(9): 5379 - 5387. [Abstract] [Full Text] [PDF]

				K. Katagiri, M. Shimonaka, and T. Kinashi Rap1-mediated Lymphocyte Function-associated Antigen-1 Activation by the T Cell Antigen Receptor Is Dependent on Phospholipase C-{gamma}1 J. Biol. Chem., March 19, 2004; 279(12): 11875 - 11881. [Abstract] [Full Text] [PDF]

				M.-A. Doucey, D. F. Legler, M. Faroudi, N. Boucheron, P. Baumgaertner, D. Naeher, M. Cebecauer, D. Hudrisier, C. Ruegg, E. Palmer, et al. The {beta}1 and {beta}3 Integrins Promote T Cell Receptor-mediated Cytotoxic T Lymphocyte Activation J. Biol. Chem., July 11, 2003; 278(29): 26983 - 26991. [Abstract] [Full Text] [PDF]

				E. J. Peterson, M. L. Woods, S. A. Dmowski, G. Derimanov, M. S. Jordan, J. N. Wu, P. S. Myung, Q.-H. Liu, J. T. Pribila, B. D. Freedman, et al. Coupling of the TCR to Integrin Activation by SLAP-130/Fyb Science, September 21, 2001; 293(5538): 2263 - 2265. [Abstract] [Full Text] [PDF]

				N. C. Ottoson, J. T. Pribila, A. S. H. Chan, and Y. Shimizu Cutting Edge: T Cell Migration Regulated by CXCR4 Chemokine Receptor Signaling to ZAP-70 Tyrosine Kinase J. Immunol., August 15, 2001; 167(4): 1857 - 1861. [Abstract] [Full Text] [PDF]

				M. L. Woods and Y. Shimizu Signaling networks regulating {beta}1 integrin-mediated adhesion of T lymphocytes to extracellular matrix J. Leukoc. Biol., June 1, 2001; 69(6): 874 - 880. [Abstract] [Full Text] [PDF]