Gérard, A.; Ghiotto, M.; Fos, C.; Guittard, G.; Compagno, D.; Galy, A.; Lemay, S.; Olive, D.; Nunès, J.A. "Dok-4 is a novel negative regulator of T cell activation" (2009) Journal of Immunology. 182(12):7681-7689
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Dok-4 (downstream of tyrosine kinase-4) is a recently identified member of the Dok family of adaptor proteins, which are characterized by an amino-terminal pleckstrin homology domain, a phosphotyrosine-binding domain, and a carboxyl-terminal region containing several tyrosines and poly-proline-rich motifs. Two members of the Dok family, Dok-1 and Dok-2, have already been described as negative regulators in T cells. However, the function of Dok-4, which is also expressed in T cells, remains unknown. In this study, we report that Dok-4 is phosphorylated after TCR engagement and shuttled within the cytoplasm of T cells before being recruited to the polarized microtubule organizing center after the formation of the immunological synapse. Loss-of-function experiments using RNA interference constructs show that Dok-4 is a negative regulator of ERK phosphorylation, IL-2 promoter activity, and T cell proliferation. Exogenous expression of wild-type Dok-4 induces a significant activation of Rap1, which is involved in the regulation of ERK. The pleckstrin homology domain of Dok-4 is required both for its cytoplasmic shuttling and relocalization as well as for its inhibitory properties on T cell activation. Thus, Dok-4 represents a novel negative regulator of T cells. Copyright © 2009 by The American Association of Immunologists, Inc.


Documento: Artículo
Título:Dok-4 is a novel negative regulator of T cell activation
Autor:Gérard, A.; Ghiotto, M.; Fos, C.; Guittard, G.; Compagno, D.; Galy, A.; Lemay, S.; Olive, D.; Nunès, J.A.
Filiación:Institut National de la Santé et de la Recherche Médicale, Centre de Recherche en Cancérologie de Marseille, Marseille, France
Institut Paoli-Calmettes, Marseille, France
Université Méditerranée, Marseille, France
Institut National de la Santé et de la Recherche Médicale, Généthon, Evry, France
Department of Medicine, Division of Nephrology, McGill University Health Centre, Montreal, QC, Canada
University of California, San Francisco, Division of Pathology, 513 Parnassus Avenue, San Francisco, CA 94143, United States
Division of Cellular Biology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle Drive, San Diego, CA 92037, United States
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Departamento de Química Biológica, Buenos Aires, Argentina
Palabras clave:downstream of tyrosine kinase 4; interleukin 2; mitogen activated protein kinase; pleckstrin; Rap1 protein; regulator protein; RNA; T lymphocyte receptor; unclassified drug; DOK4 protein, human; lymphocyte antigen receptor; phosphotyrosine; signal peptide; article; controlled study; cytoplasm; human; human cell; immunological synapse; loss of function mutation; lymphocyte proliferation; microtubule; polarization; priority journal; promoter region; protein domain; protein localization; protein phosphorylation; RNA interference; T lymphocyte activation; wild type; antigen presenting cell; cell communication; cell line; chemistry; gene expression regulation; genetics; immunology; lymphocyte activation; metabolism; microtubule organizing center; protein motif; signal transduction; T lymphocyte; Amino Acid Motifs; Antigen-Presenting Cells; Cell Communication; Cell Line; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Lymphocyte Activation; Microtubule-Organizing Center; Phosphotyrosine; Promoter Regions, Genetic; Receptors, Antigen, T-Cell; Signal Transduction; T-Lymphocytes
Página de inicio:7681
Página de fin:7689
Título revista:Journal of Immunology
Título revista abreviado:J. Immunol.
CAS:interleukin 2, 85898-30-2; mitogen activated protein kinase, 142243-02-5; RNA, 63231-63-0; phosphotyrosine, 21820-51-9; DOK4 protein, human; Intracellular Signaling Peptides and Proteins; Phosphotyrosine, 21820-51-9; Receptors, Antigen, T-Cell


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---------- APA ----------
Gérard, A., Ghiotto, M., Fos, C., Guittard, G., Compagno, D., Galy, A., Lemay, S.,..., Nunès, J.A. (2009) . Dok-4 is a novel negative regulator of T cell activation. Journal of Immunology, 182(12), 7681-7689.
---------- CHICAGO ----------
Gérard, A., Ghiotto, M., Fos, C., Guittard, G., Compagno, D., Galy, A., et al. "Dok-4 is a novel negative regulator of T cell activation" . Journal of Immunology 182, no. 12 (2009) : 7681-7689.
---------- MLA ----------
Gérard, A., Ghiotto, M., Fos, C., Guittard, G., Compagno, D., Galy, A., et al. "Dok-4 is a novel negative regulator of T cell activation" . Journal of Immunology, vol. 182, no. 12, 2009, pp. 7681-7689.
---------- VANCOUVER ----------
Gérard, A., Ghiotto, M., Fos, C., Guittard, G., Compagno, D., Galy, A., et al. Dok-4 is a novel negative regulator of T cell activation. J. Immunol. 2009;182(12):7681-7689.