Unknown

Dataset Information

0

Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation.


ABSTRACT: Murine protein serine/threonine kinase 38 (MPK38) is a member of the AMP-activated protein kinase-related serine/threonine kinase family that plays an important role in various cellular processes, including cell cycle, signaling pathways, and self-renewal of stem cells. Here we demonstrate a functional association between MPK38 and apoptosis signal-regulating kinase 1 (ASK1). The physical association between MPK38 and ASK1 was mediated through their carboxyl-terminal regulatory domains and was increased by H(2)O(2) or tumor necrosis factor alpha treatment. The use of kinase-dead MPK38 and ASK1 mutants revealed that MPK38-ASK1 complex formation was dependent on the activities of both kinases. Ectopic expression of wild-type MPK38, but not kinase-dead MPK38, stimulated ASK1 activity by Thr(838) phosphorylation and enhanced ASK1-mediated signaling to both JNK and p38 kinases. However, the phosphorylation of MKK6 and p38 by MPK38 was not detectable. In addition, MPK38-mediated ASK1 activation was induced through the increased interaction between ASK1 and its substrate MKK3. MPK38 also stimulated H(2)O(2)-mediated apoptosis by enhancing the ASK1 activity through Thr(838) phosphorylation. These results suggest that MPK38 physically interacts with ASK1 in vivo and acts as a positive upstream regulator of ASK1.

SUBMITTER: Jung H 

PROVIDER: S-EPMC3259894 | biostudies-other | 2008 Dec

REPOSITORIES: biostudies-other

altmetric image

Publications

Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation.

Jung Haiyoung H   Seong Hyun-A HA   Ha Hyunjung H  

The Journal of biological chemistry 20081023 50


Murine protein serine/threonine kinase 38 (MPK38) is a member of the AMP-activated protein kinase-related serine/threonine kinase family that plays an important role in various cellular processes, including cell cycle, signaling pathways, and self-renewal of stem cells. Here we demonstrate a functional association between MPK38 and apoptosis signal-regulating kinase 1 (ASK1). The physical association between MPK38 and ASK1 was mediated through their carboxyl-terminal regulatory domains and was i  ...[more]

Similar Datasets

| S-EPMC2804202 | biostudies-literature
| S-EPMC2945587 | biostudies-literature
| S-EPMC108879 | biostudies-literature
| S-EPMC1222342 | biostudies-other
| S-EPMC6480182 | biostudies-literature
| S-EPMC85221 | biostudies-literature
| S-EPMC3664117 | biostudies-literature
| S-EPMC8397447 | biostudies-literature
| S-EPMC4096904 | biostudies-literature
| S-EPMC6679093 | biostudies-literature