The Ca(2+)-transport ATPases from the plasma membrane.

The initial studies on the plasma membrane (PM) Ca(2+)-transport ATPases were made in the erythrocyte, a structure that can not be taken as representing a typical eukaryotic cell. In other cell types however, the study of the PM Ca(2+)-transport ATPase is complicated by the simultaneous expression of related Ca(2+)-pumps in intracellular stores. Whereas there are as yet no known specific inhibitors for the PM Ca(2+)-transport ATPase, a number of selective inhibitors for the endo(sarco)plasmic reticulum Ca2+ pumps have been described: thapsigargin, cyclopiazonic acid and 2,5-di-(tert-butyl)-1,4-benzohydroquinone. With the recent introduction of the molecular biological approach, it became quickly obvious that a family of at least 5 different PM Ca(2+)-transport ATPase genes govern the tissue-dependent expression of PM Ca2+ pumps. Moreover alternative splicing of the primary gene transcripts was found to further enhance the number of pump variants. The PM Ca(2+)-transport ATPase are subject to modulatory control by calmodulin, by acidic phospholipids, and by the known families of protein kinases. Each of the ensuing effects are mutually related and interdependent. The wide variety PM Ca2+ pump isoforms and their regulation by such an intricate modulatory network allows the distinct tissues to adapt most adequately to the prevailing tissue and stimulus specific requirements.