Cargando…
Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells
T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that is required for T cell antigen receptor (TCR)–induced cytokine synthesis in T cells. How TSAd functions in TCR signal transduction is not clear. Previous work has suggested a nucl...
Autores principales: | , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2006
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118198/ https://www.ncbi.nlm.nih.gov/pubmed/16446380 http://dx.doi.org/10.1084/jem.20051637 |
_version_ | 1782140970966450176 |
---|---|
author | Marti, Francesc Garcia, Gonzalo G. Lapinski, Philip E. MacGregor, Jennifer N. King, Philip D. |
author_facet | Marti, Francesc Garcia, Gonzalo G. Lapinski, Philip E. MacGregor, Jennifer N. King, Philip D. |
author_sort | Marti, Francesc |
collection | PubMed |
description | T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that is required for T cell antigen receptor (TCR)–induced cytokine synthesis in T cells. How TSAd functions in TCR signal transduction is not clear. Previous work has suggested a nuclear role for this adapter. However, other evidence suggests that TSAd also functions in the cytoplasm. Using T cells from TSAd-deficient mice, we now show that the major role of TSAd in the cytoplasm is in activation of the LCK protein tyrosine kinase at the outset of TCR signal transduction. Consequently, TSAd regulates several downstream signaling events, including intracellular calcium mobilization and activation of the Ras–extracellular signal–regulated kinase signaling pathway. TSAd regulates LCK activity directly through physical interaction with LCK SH3 and SH2 domains. These studies reveal TSAd as a positive regulator of proximal TCR signal transduction and provide important new information on the mechanism of TCR-induced LCK activation. |
format | Text |
id | pubmed-2118198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21181982007-12-13 Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells Marti, Francesc Garcia, Gonzalo G. Lapinski, Philip E. MacGregor, Jennifer N. King, Philip D. J Exp Med Brief Definitive Reports T cell–specific adapter protein (TSAd) is a SRC-homology-2 (SH2) domain–containing intracellular signaling molecule that is required for T cell antigen receptor (TCR)–induced cytokine synthesis in T cells. How TSAd functions in TCR signal transduction is not clear. Previous work has suggested a nuclear role for this adapter. However, other evidence suggests that TSAd also functions in the cytoplasm. Using T cells from TSAd-deficient mice, we now show that the major role of TSAd in the cytoplasm is in activation of the LCK protein tyrosine kinase at the outset of TCR signal transduction. Consequently, TSAd regulates several downstream signaling events, including intracellular calcium mobilization and activation of the Ras–extracellular signal–regulated kinase signaling pathway. TSAd regulates LCK activity directly through physical interaction with LCK SH3 and SH2 domains. These studies reveal TSAd as a positive regulator of proximal TCR signal transduction and provide important new information on the mechanism of TCR-induced LCK activation. The Rockefeller University Press 2006-02-20 /pmc/articles/PMC2118198/ /pubmed/16446380 http://dx.doi.org/10.1084/jem.20051637 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Reports Marti, Francesc Garcia, Gonzalo G. Lapinski, Philip E. MacGregor, Jennifer N. King, Philip D. Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title | Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title_full | Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title_fullStr | Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title_full_unstemmed | Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title_short | Essential role of the T cell–specific adapter protein in the activation of LCK in peripheral T cells |
title_sort | essential role of the t cell–specific adapter protein in the activation of lck in peripheral t cells |
topic | Brief Definitive Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118198/ https://www.ncbi.nlm.nih.gov/pubmed/16446380 http://dx.doi.org/10.1084/jem.20051637 |
work_keys_str_mv | AT martifrancesc essentialroleofthetcellspecificadapterproteinintheactivationoflckinperipheraltcells AT garciagonzalog essentialroleofthetcellspecificadapterproteinintheactivationoflckinperipheraltcells AT lapinskiphilipe essentialroleofthetcellspecificadapterproteinintheactivationoflckinperipheraltcells AT macgregorjennifern essentialroleofthetcellspecificadapterproteinintheactivationoflckinperipheraltcells AT kingphilipd essentialroleofthetcellspecificadapterproteinintheactivationoflckinperipheraltcells |