Unknown

Dataset Information

0

BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.


ABSTRACT: B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced B cell survival was actually independent of ERK1/2 activation but required ERK5 activation. Consistent with this, we showed that conditional deletion of ERK5 in B cells led to a pronounced global reduction in mature B2 B cell numbers, which correlated with impaired survival of ERK5-deficient B cells after BAFF stimulation. ERK5 was required for optimal BAFF up-regulation of Mcl1 and Bcl2a1, which are prosurvival members of the Bcl-2 family. However, ERK5 deficiency did not alter BAFF activation of the PI3-kinase-Akt or NF-κB signaling pathways, which are also important for BAFF to promote mature B cell survival. Our study reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF-induced mature B cell survival and homeostatic maintenance of B2 cell numbers.

SUBMITTER: Jacque E 

PROVIDER: S-EPMC4451135 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

Jacque Emilie E   Schweighoffer Edina E   Tybulewicz Victor L J VL   Ley Steven C SC  

The Journal of experimental medicine 20150518 6


B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and 2 suggested that activation of ERK 1 and 2 MAP kinases is required for BAFF-R to promote B cell survival. However, these inhibitors are now known to also inhibit MEK5, which activates the related MAP kinase ERK5. In the present study, we demonstrated that BAFF-induced B cell survival was actually i  ...[more]

Similar Datasets

| S-EPMC2664926 | biostudies-literature
| S-EPMC7069993 | biostudies-literature
| S-EPMC6370793 | biostudies-literature
| S-EPMC8538987 | biostudies-literature
| S-EPMC4628059 | biostudies-literature
| S-EPMC10622508 | biostudies-literature
| S-EPMC3726595 | biostudies-literature
| S-EPMC2373911 | biostudies-literature
| S-EPMC3465495 | biostudies-literature
| S-EPMC6186824 | biostudies-literature