Choline kinase and its functionThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

Abstract

Choline kinase (CK) was discovered in 1953. Progress in understanding the function of CK was slow until its purification in 1984. The subsequent cloning and expression of the cDNA led to the description of the gene structures. Two genes encode choline kinase, Chka and Chkb, and 3 isoforms of the enzyme have been identified — CKα-1, CKα-2, and CKβ — and the active form of CK is a hetero- or homo-dimer. More recently, gene-disrupted mice have been described. Mice that lack CKα die early in embryogenesis. In contrast, mice that lack CKβ survive to adulthood, but develop hindlimb muscular dystrophy and forelimb bone deformity. It has been shown that this hindlimb muscular dystrophy is due to decreased biosynthesis of phosphatidylcholine and increased catabolism of phosphatidylcholine in the hindlimbs, but not the forelimbs, of mice. CK and its product phosphocholine have also been implicated in development of numerous cancers. Thus, a possible treatment for some kinds of cancer may involve drug inhibition of CK or targeting the expression of CK with RNA interference. In the mid 1950s it was clear that CK was important for the biosynthesis of phosphatidylcholine, but no one predicted a role for CK in muscular dystrophy, bone deformities, or cancer.