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Noncanonical mode of ERK action controls alternative αß and γδ T cell lineage fates.
Lee, Sang-Yun; Coffey, Francis; Fahl, Shawn P; Peri, Suraj; Rhodes, Michele; Cai, Kathy Q; Carleton, Michael; Hedrick, Stephen M; Fehling, Hans Joerg; Zúñiga-Pflücker, Juan Carlos; Kappes, Dietmar J; Wiest, David L.
Afiliação
  • Lee SY; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Coffey F; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Fahl SP; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Peri S; Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Rhodes M; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Cai KQ; Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, 333 Cottman Avenue, Philadelphia, PA19111-2497, USA.
  • Carleton M; Rosetta Inpharmatics LLC, 12040 115th Avenue NE, Suite 210 Kirkland, WA 98034, USA.
  • Hedrick SM; Department of Cellular and Molecular Medicine and Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Fehling HJ; Institute of Immunology, University Clinics Ulm, 89081, Germany.
  • Zúñiga-Pflücker JC; Sunnybrook Research Institute, and the Department of Immunology, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.
  • Kappes DJ; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
  • Wiest DL; Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA. Electronic address: david.wiest@fccc.edu.
Immunity ; 41(6): 934-46, 2014 Dec 18.
Article em En | MEDLINE | ID: mdl-25526308
Gradations in extracellular regulated kinase (ERK) signaling have been implicated in essentially every developmental checkpoint or differentiation process encountered by lymphocytes. Yet, despite intensive effort, the molecular basis by which differences in ERK activation specify alternative cell fates remains poorly understood. We report here that differential ERK signaling controls lymphoid-fate specification through an alternative mode of action. While ERK phosphorylates most substrates, such as RSK, by targeting them through its D-domain, this well-studied mode of ERK action was dispensable for development of γδ T cells. Instead, development of γδ T cells was dependent upon an alternative mode of action mediated by the DEF-binding pocket (DBP) of ERK. This domain enabled ERK to bind a distinct and select set of proteins required for specification of the γδ fate. These data provide the first in vivo demonstration for the role of DBP-mediated interactions in orchestrating alternate ERK-dependent developmental outcomes.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Receptores de Antígenos de Linfócitos T gama-delta / Receptores de Antígenos de Linfócitos T alfa-beta / MAP Quinases Reguladas por Sinal Extracelular Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Receptores de Antígenos de Linfócitos T gama-delta / Receptores de Antígenos de Linfócitos T alfa-beta / MAP Quinases Reguladas por Sinal Extracelular Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article