Title | SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. |
Publication Type | Journal Article |
Year of Publication | 2008 |
Authors | Herzog S, Hug E, Meixlsperger S, Paik J-H, DePinho RA, Reth M, Jumaa H |
Journal | Nat Immunol |
Volume | 9 |
Issue | 6 |
Pagination | 623-31 |
Date Published | 2008 Jun |
ISSN | 1529-2916 |
Keywords | Adaptor Proteins, Signal Transducing, B-Lymphocytes, Forkhead Transcription Factors, Genes, Immunoglobulin Light Chain, Humans, Phosphatidylinositol 3-Kinases, Protein-Tyrosine Kinases, Recombination, Genetic |
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. |
DOI | 10.1038/ni.1616 |
Alternate Journal | Nat Immunol |
PubMed ID | 18488031 |
Related Faculty:
Ji-Hye Paik, Ph.D.