P38 MAP kinase and MAPKAP kinases MK2/3 cooperatively phosphorylate epithelial keratins.

ABSTRACT: The MAPK-activated protein kinases (MAPKAP kinases) MK2 and MK3 are directly activated via p38 MAPK phosphorylation, stabilize p38 by complex formation, and contribute to the stress response. The list of substrates of MK2/3 is increasing steadily. We applied a phosphoproteomics approach to compare protein phosphorylation in MK2/3-deficient cells rescued or not by ectopic expression of MK2. In addition to differences in phosphorylation of the known substrates of MK2, HSPB1 and Bag-2, we identified strong differences in phosphorylation of keratin 8 (K8). The phosphorylation of K8-Ser(73) is catalyzed directly by p38, which in turn shows MK2-dependent expression. Notably, analysis of small molecule p38 inhibitors on K8-Ser(73) phosphorylation also demonstrated reduced phosphorylations of kera

SUBMITTER: Menon MB 

PROVIDER: S-EPMC2963412 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature