Mice deficient for N-ras: Impaired antiviral immune response and T-cell function

Ignacio Pérez de Castro, Roberto Diaz, Marcos Malumbres, María Inmaculada Hernández, Jaishree Jagirdar, María Jiménez, Daniel Ahn, Angel Pellicer

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Ras proteins have a key role in the regulation of several cellular functions, and are involved in a significant percentage of human tumors. However, the specific functions of the different Ras isoforms are poorly understood. In this work, we show for the first time a specific role for N-ras in T-cell function and development. Mice defective for N-ras have low numbers of CD8 single positive thymocytes and decreased thymocyte proliferation in vitro. In Ras signaling and activation assays, KO-N-ras thymocytes showed a defective response to T-cell activation. In turn, these deficiencies resulted in a significant reduction in the production of interleukin 2 on thymocyte activation. We have also detected in vivo the functional consequences of N-ras deficiency. KO-N-ras mice showed an increased sensitivity to influenza infection, especially when low doses of virus were used. Finally, we have detected an abnormal activation pattern of downstream Ras molecules in T-cell receptor-activated KO-N-ras thymocytes that is consistent with the defective T-cell function found in these animals. All of the results derived from this work constitute a significant contribution to the knowledge of N-ras-specific functions.

Original languageEnglish (US)
Pages (from-to)1615-1622
Number of pages8
JournalCancer Research
Volume63
Issue number7
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Pérez de Castro, I., Diaz, R., Malumbres, M., Hernández, M. I., Jagirdar, J., Jiménez, M., Ahn, D., & Pellicer, A. (2003). Mice deficient for N-ras: Impaired antiviral immune response and T-cell function. Cancer Research, 63(7), 1615-1622.