The plasma membrane calcium pump, its role and regulation: new complexities and possibilities.
Significant progress has been achieved in elucidating the role of the plasma membrane Ca2(+)-ATPase in cellular Ca2+ homeostasis and physiology since the enzyme was first purified and physiology since the enzyme was first purified and cloned a number of years ago. The simple notion that the PM Ca2(+)-ATPase controls resting levels of [Ca2+]CYT has been challenged by the complexity arising from the finding of four major isoforms and splice variants of the Ca2+ pump, and the finding that these are differentially localized in various organs and subcellular regions. Furthermore, the isoforms exhibit differential sensitivities to Ca2+, calmodulin, ATP, and kinase-mediated phosphorylation. The latter pathways of regulation can give rise to activation or inhibition of the Ca2+ pump activity, depending on the kinase and the particular Ca2+ pump isoform. Significant progress is being made in elucidating subtle and more profound roles of the PM Ca2(+)-ATPase in the control of cellular function. Further understanding of these roles awaits new studies in both transfected cells and intact organelles, a process that will be greatly aided by the development of new and selective Ca2+ pump inhibitors.
Monteith
G R
GR
School of Pharmacy, University of Queensland, St. Lucia, Australia.
Wanigasekara
Y
Y
Roufogalis
B D
BD
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010770:Phosphotransferases / Q000494:pharmacology; D020033:Protein Isoforms / Q000502:physiology
D020033:Protein Isoforms; D010770:Phosphotransferases; D000252:Calcium-Transporting ATPases; D002118:Calcium