Control of B cell development by Ras-mediated activation of Raf

Brian M. Iritani, Katherine A. Forbush, Michael A. Farrar, Roger M. Perlmutter

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Cell fate commitment in a variety of lineages requires signals conveyed via p21(ras). To examine the role of p21(ras) in the development of B lymphocytes, we generated transgenic mice expressing a dominant-negative form of Ras in B lymphocyte progenitors, using a novel transcriptional element consisting of the Eμ enhancer and the lck proximal promoter. Expression of dominant-negative Ras arrests B cell development at a very early stage, prior to formation of the pre-B cell receptor. Furthermore, an activated form of Raf expressed in the same experimental system could both drive the maturation of normal pro-B cells and rescue development of progenitors expressing dominant-negative Ras. Hence p21(ras) normally regulates early development of B lymphocytes by a mechanism that involves activation of the serine/threonine kinase Raf.

Original languageEnglish (US)
Pages (from-to)7019-7031
Number of pages13
JournalEMBO Journal
Volume16
Issue number23
DOIs
StatePublished - Dec 1 1997

Keywords

  • B cell development
  • Raf
  • Ras
  • Transgenic mice

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