Isolation and chromosomal mapping of human glycogen synthase kinase-3α and -3β encoding genes

Abstract

Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase that exists as two isoforms, α and β, encoded by separate genes. Phosphorylation targets include a variety of cytoplasmic and nuclear proteins. Recent studies found that neurofilaments, amyloid precursor protein, and tau proteins are substrates of GSK-3 and that aberrant phosphorylation of these proteins is implicated in pathologies of the nervous system. To analyse the organisation of these two genes, a YAC library was screened by polymerase chain reaction, using primers specific for human GSK-3α and GSK-3β cDNA. TWo clones, 220 and 285 kb m size, containing the complete GSK-3α coding sequence, and two clones, 365 and 285 kb in size, containing the 5' coding sequence of GSK-3β, were isolated. By somatic cell hybrid panel DNA amplification and radiation hybrid mapping, GSK-3α was found to be located at 19q13.2. On the other hand, by somatic cell hybrid panel DNA amplification and fluorescence in situ hybridisation using the 285-kb YAC clone, GSK-3β was mapped to 3q13.3.