2. Academic Validation
  3. ALPK1 phosphorylates myosin IIA modulating TNF-α trafficking in gout flares

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

  • Sci Rep. 2016 May 12;6:25740. doi: 10.1038/srep25740.
Chi-Pin Lee 1,  Shang-Lun Chiang 2 3,  Albert Min-Shan Ko 4,  Yu-Fan Liu 5,  Che Ma 6,  Chi-Yu Lu 7,  Chung-Ming Huang 8,  Jan-Gowth Chang 9,  Tzer-Min Kuo 2,  Chia-Lin Chen 5,  Eing-Mei Tsai 1,  Ying-Chin Ko 2 10
Affiliations

Affiliations

  • 1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 2 Environment-Omics-Diseases Research Center, China Medical University Hospital, Taichung, Taiwan.
  • 3 Department of Health Risk Management, College of Public Health, China Medical University, Taichung City, Taiwan.
  • 4 Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig D-04103, Germany.
  • 5 Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan.
  • 6 Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • 7 Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 8 Graduate Institute of Integrated Medicines, China Medical University, Taichung, Taiwan.
  • 9 Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan.
  • 10 Graduate Institute of Clinical Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
PMID: 27169898 DOI: 10.1038/srep25740
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 medicated with colchicine has shown reduced Myosin IIA and TNF-α but not ALPK1. The findings suggest ALPK1 is a kinase that participates in the regulation of Golgi-derived TNF-α trafficking through Myosin IIA phosphorylation in the inflammation of gout. This novel pathway could be blocked at the level of Myosin by colchicine in gout treatment.

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