Abstract

The role of Ca2+ in the regulation of biological processes is prominently expressed in muscle, where activation is produced by a transient elevation of the myoplasmic Ca2+, followed by a reduction that brings about relaxation. This Program Project is concerned with the control of contractile activation by calcium ion in cardiac and skeletal muscle, with emphasis on the role of membranes producing Ca2+ concentration transients in the myoplasm. This renewal application includes four Component Projects, and two Component Core Units. Project 0002 (Inesi) is devoted to studies of molecular structure and function in the Ca2+ transport ATPase of sarcoplasmic reticulum;
the aim i s to clarify the molecular mechanism whereby catalytic and transport activities are coupled in this protein. Project 0007 (Fambrough-Kessler) is directed to genetic elucidation of structures and functions involved int he expression and regulation of Ca2+ ATPases in cardiac muscle, skeletal muscle, and other tissues. Project 0009 (Rogers-Lederer) deals specifically with Ca2+ transients in cardiac myocytes, and the involvement of protein kinase C in regulation of Ca2+ fluxes and contractile activation; it will also identify the substrates of protein kinase C, and follow the expression of isoforms of this kinase. Core 9001 will provide technical support in the fields of protein chemistry and molecular biology.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL027867-14
Application #
2216194
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1982-09-01
Project End
1997-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
14
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Maryland Baltimore
Department
Biochemistry
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201

  Publications

Mahoney Jr, William M; Hong, Jeong-Ho; Yaffe, Michael B et al. (2005) The transcriptional co-activator TAZ interacts differentially with transcriptional enhancer factor-1 (TEF-1) family members. Biochem J 388:217-25
Toyoshima, Chikashi; Inesi, Giuseppe (2004) Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum. Annu Rev Biochem 73:269-92
Ma, Hailun; Inesi, Giuseppe; Toyoshima, Chikashi (2003) Substrate-induced conformational fit and headpiece closure in the Ca2+ATPase (SERCA). J Biol Chem 278:28938-43
McLean, B Gail; Lee, Katherine S; Simpson, Paul C et al. (2003) Basal and alpha1-adrenergic-induced activity of minimal rat betaMHC promoters in cardiac myocytes requires multiple TEF-1 but not NFAT binding sites. J Mol Cell Cardiol 35:461-71
Sumbilla, Carlota; Lewis, David; Hammerschmidt, Tina et al. (2002) The slippage of the Ca2+ pump and its control by anions and curcumin in skeletal and cardiac sarcoplasmic reticulum. J Biol Chem 277:13900-6
Long, X; Wu, G; Gaa, S T et al. (2002) Inhibition of protein phosphatase-1 is linked to phosphorylation of p53 and apoptosis. Apoptosis 7:31-9
Hua, Suming; Inesi, Giuseppe; Nomura, Hiromi et al. (2002) Fe(2+)-catalyzed oxidation and cleavage of sarcoplasmic reticulum ATPase reveals Mg(2+) and Mg(2+)-ATP sites. Biochemistry 41:11405-10
Maeda, Tomoji; Mazzulli, Joseph R; Farrance, Iain K G et al. (2002) Mouse DTEF-1 (ETFR-1, TEF-5) is a transcriptional activator in alpha 1-adrenergic agonist-stimulated cardiac myocytes. J Biol Chem 277:24346-52
Inesi, Giuseppe; Zhang, Zhongsen; Lewis, David (2002) Cooperative setting for long-range linkage of Ca(2+) binding and ATP synthesis in the Ca(2+) ATPase. Biophys J 83:2327-32
Hua, Suming; Ma, Hailun; Lewis, David et al. (2002) Functional role of ""N"" (nucleotide) and ""P"" (phosphorylation) domain interactions in the sarcoplasmic reticulum (SERCA) ATPase. Biochemistry 41:2264-72

Showing the most recent 10 out of 118 publications