Studies of the relationship of structure and function of the Ca2+ pumping ATPase of plasma membranes will be continued. Such Ca2+ pumps exist in the plasma membranes of heart, smooth muscle, kidney, brain, intestinal epithelium and several other cell types. These pumps are involved in control of intracellular Ca2+ levels in cells such as those of smooth muscle and in movement of Ca2+ across cell layers such as the kidney tubule epithelium. Information about the regulation of these pumps may thus give information relevant to hypertension and kidney disease, among other conditions. The pump consists of a single polypeptide chain, Mr = 138,000; it is possible to obtain it pure and in reasonable quantity from human erythrocytes. We propose studies designed to create a map of the primary structure of the enzyme, and to locate the various functions of this enzyme on the map. Studies will also be carried out on the regulation of the enzyme by the lipids of the phosphatidylinositol cycle, by proteolysis, by calmodulin, and by phosphorylation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028835-12
Application #
3276173
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1980-08-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Strehler, Emanuel E (2013) Plasma membrane calcium ATPases as novel candidates for therapeutic agent development. J Pharm Pharm Sci 16:190-206
Caride, Ariel J; Bennett, Richard D; Strehler, Emanuel E (2010) Kinetic analysis reveals differences in the binding mechanism of calmodulin and calmodulin-like protein to the IQ motifs of myosin-10. Biochemistry 49:8105-16
Bajzer, Zeljko; Huzak, Miljenko; Neff, Kevin L et al. (2008) Mathematical analysis of models for reaction kinetics in intracellular environments. Math Biosci 215:35-47
Caride, Ariel J; Filoteo, Adelaida G; Penniston, John T et al. (2007) The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics: implications for Ca2+ signaling. J Biol Chem 282:25640-8
Ribiczey, Polett; Tordai, Attila; Andrikovics, Hajnalka et al. (2007) Isoform-specific up-regulation of plasma membrane Ca2+ATPase expression during colon and gastric cancer cell differentiation. Cell Calcium 42:590-605
Strehler, E E; Filoteo, A G; Penniston, J T et al. (2007) Plasma-membrane Ca(2+) pumps: structural diversity as the basis for functional versatility. Biochem Soc Trans 35:919-22
Vanagas, Laura; Rossi, Rolando C; Caride, Ariel J et al. (2007) Plasma membrane calcium pump activity is affected by the membrane protein concentration: evidence for the involvement of the actin cytoskeleton. Biochim Biophys Acta 1768:1641-9
Paszty, Katalin; Antalffy, Geza; Hegedus, Luca et al. (2007) Cleavage of the plasma membrane Ca+ATPase during apoptosis. Ann N Y Acad Sci 1099:440-50
Strehler, Emanuel E; Caride, Ariel J; Filoteo, Adelaida G et al. (2007) Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling. Ann N Y Acad Sci 1099:226-36
Kip, Sertac N; Strehler, Emanuel E (2007) Rapid downregulation of NCX and PMCA in hippocampal neurons following H2O2 oxidative stress. Ann N Y Acad Sci 1099:436-9

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