Chromosomal organization of adrenergic receptor genes.
Abstract
The adrenergic receptors (ARs) (subtypes alpha 1, alpha 2, beta 1, and beta 2) are
a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors
that mediate the physiological effects of the hormone epinephrine and the neurotransmitter
norepinephrine. We have previously assigned the genes for beta 2- and alpha 2-AR to
human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids
and in situ chromosomal hybridization, we have now mapped the alpha 1-AR gene to chromosome
5q32----q34, the same position as beta 2-AR, and the beta 1-AR gene to chromosome
10q24----q26, the region where alpha 2-AR is located. In mouse, both alpha 2- and
beta 1-AR genes were assigned to chromosome 19, and the alpha 1-AR locus was localized
to chromosome 11. Pulsed field gel electrophoresis has shown that the alpha 1- and
beta 2-AR genes in humans are within 300 kilobases (kb) and the distance between the
alpha 2- and beta 1-AR genes is less than 225 kb. The proximity of these two pairs
of AR genes and the sequence similarity that exists among all the ARs strongly suggest
that they are evolutionarily related. Moreover, they likely arose from a common ancestral
receptor gene and subsequently diverged through gene duplication and chromosomal duplication
to perform their distinctive roles in mediating the physiological effects of catecholamines.
The AR genes thus provide a paradigm for understanding the evolution of such structurally
conserved yet functionally divergent families of receptor molecules.
Type
Journal articleSubject
AnimalsBiological Evolution
Blotting, Southern
Cell Line
Cells, Cultured
Chromosome Banding
Chromosome Mapping
Chromosomes, Human
Cricetinae
Cricetulus
DNA
Fibroblasts
Humans
Hybrid Cells
Lymphocytes
Mice
Nucleic Acid Hybridization
Receptors, Adrenergic, alpha
Receptors, Adrenergic, beta
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Marc G. Caron
James B. Duke Distinguished Professor of Cell Biology
Studies of the mechanisms of action and regulation of hormones and neurotransmitters
at the cellular and molecular levels constitute the main goals our of research activities.
G protein-coupled receptors (GPCR) mediate the actions of signaling molecules from
unicellular organisms to man. We have used adrenergic and dopamine receptors to characterize
the structure/function and regulation mechanisms of these prototypes of G protein-coupled
receptors. Another approach has been to characterize
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Robert J. Lefkowitz
The Chancellor's Distinguished Professor of Medicine
Dr. Lefkowitz’s memoir, A Funny Thing Happened on the Way to Stockholm, recounts his
early career as a cardiologist and his transition to biochemistry, which led to his
Nobel Prize win.
Robert J. Lefkowitz, M.D. is James B. Duke Professor of Medicine and Professor of
Biochemistry and Chemistry at the Duke University Medical Center. He has been an Investigator
of the
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