HUMAN BILIARY EPITHELIAL-CELL LINE MZ-CHA-1 EXPRESSES NEW ISOFORMS OF CALMODULIN-DEPENDENT PROTEIN-KINASE-II

Background & Aims: Calmodulin-dependent protein kinase II is a family of closely related multimeric enzymes that regulate a wide variety of cellular processes. In biliary epithelial cells, this kinase seems to regulate Ca2+-dependent Cl- currents. The aim of this study was to identify isoforms of this kinase expressed in biliary cells. Methods: Sequencing of reverse-transcription polymerase chain reaction products identified multiple isoforms in Mz-ChA-1 cells. Results: Two previously identified isoforms (gamma B and gamma C) and three new isoforms (gamma D, gamma E, and gamma F) of calmodulin-dependent protein kinase II were identified. Each of the novel isoforms contains a unique insert of 114 base pairs in the association region. This insert lies outside the previously identified variable region. In addition, gamma D and gamma F contained other deletions (42 and 69 base pairs, respectively) in the variable region. These isoforms are expressed in a variety of tissues, including biliary epithelial and gallbladder cells, but only gamma C is expressed in rat hepatocytes. Conclusions: Identification of these biliary kinase isoforms paves the way for future studies that will elucidate the role of individual isozymes in agonist-stimulated biliary Cl- and fluid secretion.