THE PLASMA-MEMBRANE CALCIUM-PUMP - FUNCTIONAL DOMAINS, REGULATION OF THE ACTIVITY, AND TISSUE-SPECIFICITY OF ISOFORM EXPRESSION

The plasma membrane Ca2+ pump is responsible for the fine regulation o f the intracellular Ca2+ level and is thus involved in the control of several cellular processes. The activity of the pump is regulated by a multiplicity of mechanisms, among which are calmodulin, acidic phosph olipids, kinase-mediated phosphorylation, or an oligomerization proces s. The C-terminal part of the molecule interacts with the region of th e pump close to the active site, leading to the decrease of the activi ty in the resting state. Four genes coding for different isoforms of t he plasma membrane Ca2+ ATPase are known in humans. Isoform 1 and 4 re present housekeeping isoforms, whereas isoforms 2 and 3 are only prese nt in specialized tissues. The variability of the protein is further i ncreased by alternative RNA splicing at two sites (A, C). Alternative splicing occurs within (splice site C) or near (splice site A) regions coding for regulatory domains of the protein. In all isoforms a corre sponding splice form exists at both splice sites. These common splice forms are present in all tissues, whereas isoform unique splice forms are normally only present in specialized tissues. In neuronal tissues all isoforms and almost the complete set of splice forms are found. Th e transcripts of the different isoforms are distributed in a region-sp ecific manner in neuronal tissues. (C) 1991 John Wiley & Sons, Inc.