title: Molecular structure and differential function of choline kinases CHKα and CHKβ in musculoskeletal system and cancer.
abstract: Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction. Choline Kinase consists of three isoforms, CHKα1, CHKα2 and CHKβ, encoded by two separate genes (CHKA(Human)/Chka(Mouse) and CHKB(Human)/Chkb(Mouse)). Both isoforms have similar structures and enzyme activity, but display some distinct molecular structural domains and differential tissue expression patterns. Whilst Choline Kinase was discovered in early 1950, its pivotal role in the development of muscular dystrophy, bone deformities, and cancer has only recently been identified. CHKα has been proposed as a cancer biomarker and its inhibition as an anti-cancer therapy. In contrast, restoration of CHKβ deficiency through CDP-choline supplements like citicoline may be beneficial for the treatment of muscular dystrophy, bone metabolic diseases, and cognitive conditions. The molecular structure and expression pattern of Choline Kinase, the differential roles of Choline Kinase isoforms and their potential as novel therapeutic targets for muscular dystrophy, bone deformities, cognitive conditions and cancer are discussed.
authors: School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Sports Science, Wenzhou Medical University, Wenzhou, 325035, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
authors: Xi
authors: X
authors: Chen
authors: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
authors: Heng
authors: H
authors: Qiu
authors: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
authors: Chao
authors: C
authors: Wang
authors: School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
authors: Yu
authors: Y
authors: Yuan
authors: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia.
authors: Jennifer
authors: J
authors: Tickner
authors: School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Western Australia, 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.
authors: Jiake
authors: J
authors: Xu
authors: School of Kinesiology, Shanghai University of Sport, Shanghai 200438, PR China. Electronic address: junzou@sus.edu.cn.
authors: Jun
authors: J
authors: Zou
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002797:Choline Kinase / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008659:Metabolic Diseases / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009136:Muscular Dystrophies / Q000188:drug therapy; D009141:Musculoskeletal System / Q000201:enzymology* / Q000503:physiopathology; D009369:Neoplasms / Q000201:enzymology* / Q000503:physiopathology
chemical_list: D014408:Biomarkers, Tumor; C517212:CHKA protein, human; C542592:CHKB protein, human; D002797:Choline Kinase
keywords: CHKα; CHKβ; Cancer; Choline kinase; Musculoskeletal system