BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells

Kevin L. Otipoby, Yoshiteru Sasaki, Marc Schmidt-Supprian, Alina Patke, Ralph Gareus, Manolis Pasparakis, Alexander Tarakhovsky, Klaus Rajewsky

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

B cell activating factor (BAFF) signals through BAFF-R to promote mature B cell survival. Recent analyses of BAFF-induced signaling revealed direct association between augmented B cell metabolic fitness and activation of Akt, one of the key regulators of cell survival. The strongest and most reproducible induction of Akt occurs with significant delay (24 h) after BAFF treatment, where it precedes activation of anabolism. It was also recently shown that BAFF induces sustained Erk activation and increased turnover of the proapoptotic molecule Bim. Here we show that these BAFF-induced signaling pathways are mediated by BAFF-R and represent previously unknown arms of I kappa B kinase (IKK)1-dependent signaling. In combination with the known role of IKK1 in regulating transcription of prosurvival genes, our data underscore the central role of IKK1 in coordinating multiple BAFF-R-mediated signaling pathways controlling mature B cell homeostasis.

Original languageEnglish
Pages (from-to)12435-12438
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number34
DOIs
StatePublished - 26 Aug 2008
Externally publishedYes

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