Biogenesis: plasma membrane calcium ATPase: 15 years of work on the purified enzyme

Abstract

The plasma membrane calcium pump is the system that ejects Ca2+ out of eukaryotic cells: this is documented in all animal and plant cells, although knowledge on the latter is only now beginning to be established. Information on lower eukaryotic cells, e.g., yeast, is still scarce, but it also is beginning to develop. The pump shares the catalytic properties of ion-motive ATPases of the P-type family, but has distinctive regulation properties: it is modulated by calmodulin, acidic phospholipids, a number of protein kinases, possibly by the interaction of calcium with its COOH-terminal region, and by aggregation (dimerization) through the calmodulin binding domain. The latter acts as an endogenous inhibitor of pump activity, much as phospholamban does for the sarcoplasmic reticulum pump. The analogy of the regulation mechanisms of the two pumps is heightened by the finding that phosphorylation of the calmodulin binding domain by protein kinase C removes its autoinhibiting function, as other kinases do in the case of phospholamban. The pump is the product of a family of four genes located on different human chromosomes. The isoform diversity is dramatically enhanced by alternative splicing of the transcripts, occurring at "hot spot" A (NH2-terminal) and C (COOH-terminal). At present more than 20 different transcripts with striking tissue and developmental specificity have been detected.