SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Academic Article uri icon

Overview

abstract

  • Although the essential role of the adaptor protein SLP-65 in pre-B cell differentiation is established, the molecular mechanism underlying its function is poorly understood. In this study, we uncover a link between SLP-65-dependent signaling and the phosphoinositide-3-OH kinase (PI(3)K)-protein kinase B (PKB)-Foxo pathway. We show that the forkhead box transcription factor Foxo3a promotes light chain rearrangement in pre-B cells. Our data suggest that PKB suppresses light chain recombination by phosphorylating Foxo proteins, whereas reconstitution of SLP-65 function counteracts PKB activation and promotes Foxo3a and Foxo1 activity in pre-B cells. Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection.

publication date

  • June 1, 2008

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • B-Lymphocytes
  • Forkhead Transcription Factors
  • Genes, Immunoglobulin Light Chain
  • Protein-Tyrosine Kinases

Identity

Scopus Document Identifier

  • 44049101651

Digital Object Identifier (DOI)

  • 10.1038/ni.1616

PubMed ID

  • 18488031

Additional Document Info

volume

  • 9

issue

  • 6