The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain.
Abstract
The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied
beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating
adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect
a general molecular mechanism operative on many G-protein-coupled receptor systems
and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding
beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular
distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined
in brain by in situ hybridization and by immunohistochemistry at the light and electron
microscopic levels. The beta ARK isozymes were found to be expressed primarily in
neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2
immunoreactivities were present both in association with postsynaptic densities and,
presynaptically, with axon terminals. The beta ARK isozymes have a regional and subcellular
distribution consistent with a general role in the desensitization of synaptic receptors.
Type
Journal articleSubject
Amino Acid SequenceAnimals
Brain
Brain Chemistry
Cyclic AMP-Dependent Protein Kinases
GTP-Binding Proteins
Molecular Sequence Data
Proteins
Rats
Synapses
beta-Adrenergic Receptor Kinases
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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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