ALPK1 phosphorylates myosin IIA modulating TNF-α trafficking in gout flares.

ABSTRACT: Gout is characterized by the monosodium urate monohydrate (MSU)-induced arthritis. Alpha kinase-1 (ALPK1) has shown to be associated with MSU-induced inflammation and gout. Here, we used bioinformatics, proteomics, cell models, and twenty in vitro human assays to clarify some of its role in the inflammatory response to MSU. We found myosin IIA to be a frequent interacting protein partner of ALPK1, binding to its N-terminal and forming a protein complex with calmodulin and F-actin, and that MSU-induced ALPK1 phosphorylated the myosin IIA. A knockdown of endogenous ALPK1 or myosin IIA significantly reduced the MSU-induced secretion of tumour necrosis factor (TNF)-α. Furthermore, all gouty patients expressed higher basal protein levels of ALPK1, myosin IIA, and plasma TNF-α, however those med

SUBMITTER: Lee CP 

PROVIDER: S-EPMC4864424 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature