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  SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway

Herzog, S., Hug, E., Meixlsperger, S., Paik, J.-H., dePinho, R. A., Reth, M., et al. (2008). SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Nature Immunology, 9, 623-631.

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 Creators:
Herzog, Sebastian1, Author           
Hug, Eva1, Author           
Meixlsperger, Sonja2, Author
Paik, Ji-Hye, Author
dePinho, Ronald A., Author
Reth, Michael1, Author           
Jumaa, Hassan1, Author           
Affiliations:
1Research Group and Chair of Molecular Immunology of the University of Freiburg, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243645              
2Max Planck Society, ou_persistent13              

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 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.

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Language(s): eng - English
 Dates: 2008-07
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 400590
 Degree: -

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Title: Nature Immunology
  Alternative Title : Nat. Immunol.
Source Genre: Journal
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Pages: - Volume / Issue: 9 Sequence Number: - Start / End Page: 623 - 631 Identifier: -