Erk Kinases Link Pre-B Cell Receptor Signaling to Transcriptional Events Required for Early B Cell Expansion

Tomoharu Yasuda, Hideki Sanjo, Gilles Pagès, Yohei Kawano, Hajime Karasuyama, Jacques Pouysségur, Masato Ogata, Tomohiro Kurosaki

Research output: Contribution to journalArticlepeer-review

113 Citations (Scopus)

Abstract

The pre-B cell receptor (pre-BCR) plays a crucial role in the development of immature B cells. Although certain aspects of proximal pre-BCR signaling have been studied, the intermediate signal transducers and the distal transcription modulators are poorly characterized. Here, we demonstrate that deletion of both Erk1 and Erk2 kinases was associated with defective pre-BCR-mediated cell expansion as well as a block in the transition of pro-B to pre-B cells. Phosphorylation of transcription factors Elk1 and CREB was mediated by Erk, and a dominant-negative mutation in the Erk-mediated phosphorylation sites of Elk1 or CREB suppressed pre-BCR-mediated cell expansion as well as expression of genes including Myc, which is involved in the cell-cycle progression. Together, our results identify a crucial role for Erk kinases in regulating B cell development by initiating transcriptional regulatory network and thereby pre-BCR-mediated cell expansion.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalImmunity
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 11 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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