@article{6ffbe070489c45aea40eb3ae5281c237,
title = "SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway",
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.",
author = "Sebastian Herzog and Eva Hug and Sonja Meixlsperger and Paik, {Ji Hye} and DePinho, {Ronald A.} and Michael Reth and Hassan Jumaa",
note = "Funding Information: We thank C. Eschbach and I. Fiedler for technical assistance, A. Wuerch for cell sorting, P.J. Nielsen for critical discussion, B.A. Hemmings (Friedrich Miescher Institute for Biomedical Research) for the cDNA encoding a myristoylated PKB, W.S. Pear (University of Pennsylvania School of Medicine) for pMIG, B.M.T. Burgering (University Medical Center Utrecht) for a plasmid containing the Foxo3a-A3 construct, and R.Y. Tsien (University of California San Diego) for the tdTomato construct. Supported by the Claudia Adam Barr Foundation and the Damon Runyon Cancer Research Foundation (J.-H.P.), the Robert A. and Funding Information: Renee E. Belfer Foundation for Innovative Cancer Science (R.A.D.), the Deutsche Forschungsgemeinschaft (SFB620 and SFB746) and the Excellence Initiative of the German federal and state governments (EXC294).",
year = "2008",
month = jun,
doi = "10.1038/ni.1616",
language = "English (US)",
volume = "9",
pages = "623--631",
journal = "Nature Immunology",
issn = "1529-2908",
publisher = "Nature Publishing Group",
number = "6",
}