A beta-adrenergic receptor kinase-like enzyme is involved in olfactory signal termination.
Abstract
We have previously shown that second-messenger-dependent kinases (cAMP-dependent kinase,
protein kinase C) in the olfactory system are essential in terminating second-messenger
signaling in response to odorants. We now document that subtype 2 of the beta-adrenergic
receptor kinase (beta ARK) is also involved in this process. By using subtype-specific
antibodies to beta ARK-1 and beta ARK-2, we show that beta ARK-2 is preferentially
expressed in the olfactory epithelium in contrast to findings in most other tissues.
Heparin, an inhibitor of beta ARK, as well as anti-beta ARK-2 antibodies, (i) completely
prevents the rapid decline of second-messenger signals (desensitization) that follows
odorant stimulation and (ii) strongly inhibits odorant-induced phosphorylation of
olfactory ciliary proteins. In contrast, beta ARK-1 antibodies are without effect.
Inhibitors of protein kinase A and protein kinase C also block odorant-induced desensitization
and phosphorylation. These data suggest that a sequential interplay of second-messenger-dependent
and receptor-specific kinases is functionally involved in olfactory desensitization.
Type
Journal articleSubject
AnimalsAntibodies
Cerebral Cortex
Chemoreceptor Cells
Cilia
Cyclic AMP-Dependent Protein Kinases
Epithelium
Heparin
Immune Sera
Kinetics
Odorants
Olfactory Pathways
Organ Specificity
Phosphorylation
Protein Kinase Inhibitors
Protein Kinases
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta
Signal Transduction
Smell
Time Factors
beta-Adrenergic Receptor Kinases
Permalink
http://hdl.handle.net/10161/7848Collections
More Info
Show full item recordScholars@Duke
Robert J. Lefkowitz
James B. Duke Professor of Medicine
The focus of work in this laboratory is on the elucidation of the molecular properties
and regulatory mechanisms controlling the function of G protein-coupled receptors.
As model systems we utilize the so called adrenergic receptors for adrenaline and
related molecules. The goal is to learn the general principles of signal transduction
from the outside to the inside of the cell which are involved in systems as diverse
as sensory perception, neuro- transmitter and hormonal signaling. Stud
Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
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