Abstract

Progress has been made toward the sequential resolution and reconstitution of specific components of a hormone-sensitive adenylate cyclase system by a combination of biochemical and genetic manipulations. These studies will be extended toward the ultimate goal of elucidation of the mechanisms of interaction of these components and of the regulation of their interactions by hormones (such as Beta-adrenergic agonists and prostaglandins), regulatory purine nucleotides, and adventitious compounds such as fluoride and cholera toxin. Individual components of the system will be purified by conventional and/or immunological techniques, and they will be characterized in isolation as a prelude toward meaningful description of their interactions. Assays of increasing precision for individual components of the system will, in addition, allow exploration of mechanisms of more chronic regulation of the rate of synthesis of cyclic AMP.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
9R01GM034497-05
Application #
3285608
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1985-01-01
Project End
1989-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Thomas, Celestine J; Tall, Gregory G; Adhikari, Anirban et al. (2008) Ric-8A catalyzes guanine nucleotide exchange on G alphai1 bound to the GPR/GoLoco exchange inhibitor AGS3. J Biol Chem 283:23150-60
Kumar, Premlata; Wu, Qian; Chambliss, Ken L et al. (2007) Direct Interactions with G alpha i and G betagamma mediate nongenomic signaling by estrogen receptor alpha. Mol Endocrinol 21:1370-80
Gibson, Scott K; Gilman, Alfred G (2006) Gialpha and Gbeta subunits both define selectivity of G protein activation by alpha2-adrenergic receptors. Proc Natl Acad Sci U S A 103:212-7
Krumins, Andrejs M; Gilman, Alfred G (2006) Targeted knockdown of G protein subunits selectively prevents receptor-mediated modulation of effectors and reveals complex changes in non-targeted signaling proteins. J Biol Chem 281:10250-62
Tall, Gregory G; Gilman, Alfred G (2005) Resistance to inhibitors of cholinesterase 8A catalyzes release of Galphai-GTP and nuclear mitotic apparatus protein (NuMA) from NuMA/LGN/Galphai-GDP complexes. Proc Natl Acad Sci U S A 102:16584-9
Malik, Sundeep; Ghosh, Mousumi; Bonacci, Tabetha M et al. (2005) Ric-8 enhances G protein betagamma-dependent signaling in response to betagamma-binding peptides in intact cells. Mol Pharmacol 68:129-36
Krumins, Andrejs M; Barker, Sheryll A; Huang, Chunfa et al. (2004) Differentially regulated expression of endogenous RGS4 and RGS7. J Biol Chem 279:2593-9
Chen, Zhu; Raman, Malavika; Chen, Linda et al. (2003) TAO (thousand-and-one amino acid) protein kinases mediate signaling from carbachol to p38 mitogen-activated protein kinase and ternary complex factors. J Biol Chem 278:22278-83
Tall, Gregory G; Krumins, Andrejs M; Gilman, Alfred G (2003) Mammalian Ric-8A (synembryn) is a heterotrimeric Galpha protein guanine nucleotide exchange factor. J Biol Chem 278:8356-62
Hooks, Shelley B; Waldo, Gary L; Corbitt, James et al. (2003) RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity. J Biol Chem 278:10087-93

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