title: ZAKβ antagonizes and ameliorates the cardiac hypertrophic and apoptotic effects induced by ZAKα.
abstract: ZAK (sterile alpha motif and leucine zipper containing kinase AZK), a serine/threonine kinase with multiple biochemical functions, has been associated with various cell processes, including cell proliferation, cell differentiation, and cardiac hypertrophy. In our previous reports, we found that the activation of ZAKα signaling was critical for cardiac hypertrophy. In this study, we show that the expression of ZAKα activated apoptosis through both a FAS-dependent pathway and a mitochondria-dependent pathway by subsequently inducing caspase-3. ZAKβ, an isoform of ZAKα, is dramatically expressed during cardiac hypertrophy and apoptosis. The interaction between ZAKα and ZAKβ was demonstrated here using immunoprecipitation. The results show that ZAKβ has the ability to diminish the expression level of ZAKα. These findings reveal an inherent regulatory role of ZAKβ to antagonize ZAKα and to subsequently downregulate the cardiac hypertrophy and apoptosis induced by ZAKα.
authors.affiliation: Graduate Institute of Aging Medicine, China Medical University, Taichung, Taiwan.|Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan.|Department of Emergency Medicine, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chien-Yao
authors.initials: CY
authors.lastname: Fu
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.|Chinese Medicine Department, China Medical University Beigang Hospital, Taiwan.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Department of Dermatology, Taipei City Hospital, Renai Branch, Taipei, Taiwan.|Center for General Education, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wen
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Ling-Chun
authors.initials: LC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Tseng
authors.affiliation: Department of Nursing, National Taichung University of Science and Technology, Taichung, Taiwan.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Hung
authors.affiliation: Department of Biotechnology, Bharathiar University, Coimbatore, India.
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: School of Dentistry, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Jaw-Ji
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan.|Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology*; D002470:Cell Survival; D042541:Intracellular Space / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D020930:MAP Kinase Kinase Kinases
chemical_list: D011494:Protein Kinases; C542928:Map3k20 protein, rat; D020930:MAP Kinase Kinase Kinases
keywords: ZAKα; ZAKβ; cardiac apoptosis; cardiac hypertrophy; sterile alpha motif and leucine zipper containing kinase