BAFF activates Akt and Erk through BAFF-R in an IKK1-dependent manner in primary mouse B cells.
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.
Otipoby
Kevin L
KL
Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Sasaki
Yoshiteru
Y
Schmidt-Supprian
Marc
M
Patke
Alina
A
Gareus
Ralph
R
Pasparakis
Manolis
M
Tarakhovsky
Alexander
A
Rajewsky
Klaus
K
D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D048429:Cell Size; D002478:Cells, Cultured; D006706:Homeostasis; D051550:I-kappa B Kinase / Q000378:metabolism*; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; D048052:Mitogen-Activated Protein Kinase 3