Abstract

The objective of this project is the elucidation of the structural determinants leading to specific high-affinity binding of hCG to its receptor and the mechanism of ligand-mediated receptor activation. There are two major aims, namely 1) Delineation of hormone and receptor binding determinants and 2) Elucidating the mechanism of receptor activation and transmembrane signaling. Site-directed mutagenesis of alpha subunit, hCG-beta, and LH/CG receptor will be used to test the hypothesis that discrete regions of hCG and of receptor are responsible for high-affinity binding. The investigations will exploit a hormone-receptor polypeptide fusion technique to construct a putative mini-gonadotropin. Receptor mutagenesis studies will be utilized to test the hypothesis that transmembrane helices 6 and 7 contain amino acid residues that are important in signaling but not ligand binding.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK033973-19
Application #
6380493
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Sato, Sheryl M
Project Start
1983-09-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
19
Fiscal Year
2001
Total Cost
$374,260
Indirect Cost

  Institution

Name
University of Georgia
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Athens
State
GA
Country
United States
Zip Code
30602

  Publications

Chen, Tsuey-Ming; Czerwiec, Frank S; Puett, David (2016) Steroidogenesis and early response gene expression in MA-10 Leydig tumor cells following heterologous receptor down-regulation and cellular desensitization. Biochem Biophys Rep 5:305-312
Cui, Juan; Yin, Yanbin; Ma, Qin et al. (2015) Comprehensive characterization of the genomic alterations in human gastric cancer. Int J Cancer 137:86-95
Bowman, Paula B; Puett, David (2014) Electron paramagnetic resonance spectroscopy of nitroxide-labeled calmodulin. Protein J 33:267-77
Cui, Juan; Xu, Ying; Puett, David (2013) Microarray-based transcriptome profiling of ovarian cancer cells. Methods Mol Biol 1049:119-37
Cui, Juan; Miner, Brooke M; Eldredge, Joanna B et al. (2011) Regulation of gene expression in ovarian cancer cells by luteinizing hormone receptor expression and activation. BMC Cancer 11:280
Angelova, Krassimira; Felline, Angelo; Lee, Moon et al. (2011) Conserved amino acids participate in the structure networks deputed to intramolecular communication in the lutropin receptor. Cell Mol Life Sci 68:1227-39
DeMars, Geneva; Fanelli, Francesca; Puett, David (2011) The extreme C-terminal region of G?s differentially couples to the luteinizing hormone and beta2-adrenergic receptors. Mol Endocrinol 25:1416-30
Cui, Juan; Eldredge, Joanna B; Xu, Ying et al. (2011) MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone. PLoS One 6:e21730
Puett, David; Angelova, Krassimira; da Costa, Marcelo Rocha et al. (2010) The luteinizing hormone receptor: insights into structure-function relationships and hormone-receptor-mediated changes in gene expression in ovarian cancer cells. Mol Cell Endocrinol 329:47-55
Puett, David; Angelova, Krassimira (2009) Determining the affinity of hormone-receptor interaction. Methods Mol Biol 590:1-20

Showing the most recent 10 out of 83 publications