Abstract

One form of signal transduction involves a number of proteins that regulate cyclic nucleotide levels in cells in response to the interaction of cell-surface receptors with specific ligands. These transducing proteins (G proteins) mediate the effects of hormones, neurotransmitters and sensory stimuli. In order to understand the function, distribution and structure of these proteins, we will isolate the DNA that encodes them. The DNA will be used to probe the structure of the gene family that encodes G proteins and the nature of the tissue-specific expression of these genes. We will start by isolating cDNA clones that correspond to the Alpha, Beta and Gamma subunits of visual transducin. We will characterize these cDNAs and use them to isolate tissue-specific cDNA clones and genomic clones that cross hybridize with transducin. We will characterize this gene family with respect to the tissues in which different genes get expressed and the mechanisms involved in specific gene expression. We will use the probes to examine variants that are defective in G protein function. We will develop an expression system to allow the cloned genes to be expressed in variant cell lines. Finally, we will introduce specific nucleotide changes in the cloned DNA and study the behavior of the modified gene products.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034236-03
Application #
3284866
Study Section
Molecular Biology Study Section (MBY)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125

  Publications

Pero, Ralph S; Borchers, Michael T; Spicher, Karsten et al. (2007) Galphai2-mediated signaling events in the endothelium are involved in controlling leukocyte extravasation. Proc Natl Acad Sci U S A 104:4371-6
Hwang, Jong-Ik; Choi, Sangdun; Fraser, Iain D C et al. (2005) Silencing the expression of multiple Gbeta-subunits eliminates signaling mediated by all four families of G proteins. Proc Natl Acad Sci U S A 102:9493-8
Hwang, Jong-Ik; Fraser, Iain D C; Choi, Sangdun et al. (2004) Analysis of C5a-mediated chemotaxis by lentiviral delivery of small interfering RNA. Proc Natl Acad Sci U S A 101:488-93
Slice, Lee W; Han, Sang-Kyou; Simon, Melvin I (2003) Galphaq signaling is required for Rho-dependent transcriptional activation of the cyclooxygenase-2 promoter in fibroblasts. J Cell Physiol 194:127-38
Bastiani, Carol A; Gharib, Shahla; Simon, Melvin I et al. (2003) Caenorhabditis elegans Galphaq regulates egg-laying behavior via a PLCbeta-independent and serotonin-dependent signaling pathway and likely functions both in the nervous system and in muscle. Genetics 165:1805-22
Han, Sang-Kyou; Dong, Xinzhong; Hwang, Jong-Ik et al. (2002) Orphan G protein-coupled receptors MrgA1 and MrgC11 are distinctively activated by RF-amide-related peptides through the Galpha q/11 pathway. Proc Natl Acad Sci U S A 99:14740-5
Dong, X; Han, S; Zylka, M J et al. (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell 106:619-32
Offermanns, S; Negulescu, P; Hu, Y H et al. (2001) Conditionally expressed G alpha 15 couples to endogenous receptors in GH3 cells. Naunyn Schmiedebergs Arch Pharmacol 364:140-8
Kabarowski, J H; Feramisco, J D; Le, L Q et al. (2000) Direct genetic demonstration of G alpha 13 coupling to the orphan G protein-coupled receptor G2A leading to RhoA-dependent actin rearrangement. Proc Natl Acad Sci U S A 97:12109-14
Hurowitz, E H; Melnyk, J M; Chen, Y J et al. (2000) Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes. DNA Res 7:111-20

Showing the most recent 10 out of 53 publications