Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization

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Item Type:	Article
Title:	Linker for activation of T cells, zeta-associated protein-70, and Src homology 2 domain-containing leukocyte protein-76 are required for TCR-induced microtubule-organizing center polarization
Creators Name:	Kuhné, M.R., Lin, J., Yablonski, D., Mollenauer, M.N., Ehrlich, L.I.R., Huppa, J., Davis, M.M. and Weiss, A.
Abstract:	Engagement of the T cell with Ag on an APC results in a series of immediate signaling events emanating from the stimulation of the TCR. These events include the induced phosphorylation of a number of cellular proteins with a subsequent increase in intracellular calcium and the restructuring of the microtubule and actin cytoskeleton within the T cell. This restructuring of the cytoskeleton culminates in the polarization of the T cell's secretory apparatus toward the engaging APC, allowing the T cell to direct secretion of cytokines toward the appropriate APC. This polarization can be monitored by analyzing the position of the microtubule-organizing center (MTOC), as it moves toward the interface of the T cell and APC. The requirements for MTOC polarization were examined at a single-cell level by studying the interaction of a Jurkat cell line expressing a fluorescently labeled MTOC with Staphylococcal enterotoxin superantigen-bound Raji B cell line, which served as the APC. We found that repolarization of the MTOC substantially followed fluxes in calcium. We also used immobilized anti-TCR mAb and Jurkat signaling mutants, defective in TCR-induced calcium increases, to determine whether signaling components that are necessary for a calcium response also play a role in MTOC polarization. We found that zeta-associated protein-70 as well as its substrate adaptor proteins linker for activation of T cells and Src homology 2 domain-containing leukocyte protein-76 are required for MTOC polarization. Moreover, our studies revealed that a calcium-dependent event not requiring calcineurin or calcium/calmodulin-dependent kinase is required for TCR-induced polarization of the MTOC.
Keywords:	Signal Transducing Adaptor Proteins, Monoclonal Antibodies, Antigen-Presenting Cells, Benzylamines, CD3 Complex, Calcineurin, Calcineurin Inhibitors, Calcium, Calcium Signaling, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Polarity, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Microtubule-Organizing Center, Phosphoproteins, Protein-Tyrosine Kinases, T-Cell Antigen Receptors, Sulfonamides, T-Lymphocytes, Tacrolimus, Cultured Tumor Cells, ZAP-70 Protein-Tyrosine Kinase
Source:	Journal of Immunology
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Volume:	171
Number:	2
Page Range:	860-6
Date:	15 July 2003
Official Publication:	https://doi.org/10.4049/jimmunol.171.2.860
PubMed:	View item in PubMed

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