Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. II. Preferential coupling of the alpha 2C-adrenergic receptor to the guanine nucleotide-binding protein, Go

Coupry, I.; Duzic, E.; Lanier, S.M.

Journal of Biological Chemistry 267(14): 9852-9857

1992


ISSN/ISBN: 0021-9258
PMID: 1349607
Accession: 007341684

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Abstract
Cell to cell communication by many hormones and neurotransmitters involves three major entities: receptor (R), G-protein (G), and effector molecule (E). Plasticiity in this system is conferred by the existence of each entity as isoforms or closely related subtypes that are expressed in a tissue-specific and developmentally regulated manner. Factors that determine signal specificity in this system are poorly understood. Such factors include the relative affinity and stoichiometry of R-G or G-E and the possible colocalization of R-G-E in cellular microdomains. Utilizing the .alpha.2-adrenergic receptor (.alpha.2-AR) system as a representative subfamily of this class of signal transducers, we determined the relative importance of these factors. By analysis of R-G coupling in mammalian cells cotransfected with .alpha.2-AR genes and G.alpha. cDNA, we demonstrate preferential coupling between an .alpha.2-AR subtype and Go. Our data implicate R-G affinity as an important determinant of signal transduction specificity and indicate that a critical level of Go.alpha. is required for coupling. This report indicates the utility of R-G cotransfection in mammalian cells as a "natural environment model" to characterized events occurring at the R-G and G-E interface.