Circulation Research. 2002;91:672-680
doi: 10.1161/01.RES.0000037000.74258.03
doi: 10.1161/01.RES.0000037000.74258.03
© 2002 American Heart Association, Inc.
Reviews |
Regulation of G Protein–Coupled Receptor Signaling by Scaffold Proteins
From the Department of Pharmacology (R.A.H.), Emory University School of Medicine, Atlanta, Ga; and the Departments of Medicine and Biochemistry (R.J.L.), Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC.
Correspondence to Robert Lefkowitz, MD, Duke University, Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Box 3821, Durham, NC 27710. E-mail lefko001{at}receptor-biol.duke.edu
The actions of many hormones and neurotransmitters are mediated through stimulation of G protein–coupled receptors. A primary mechanism by which these receptors exert effects inside the cell is by association with heterotrimeric G proteins, which can activate a wide variety of cellular enzymes and ion channels. G protein–coupled receptors can also interact with a number of cytoplasmic scaffold proteins, which can link the receptors to various signaling intermediates and intracellular effectors. The multicomponent nature of G protein–coupled receptor signaling pathways makes them ideally suited for regulation by scaffold proteins. This review focuses on several specific examples of G protein–coupled receptor-associated scaffolds and the roles they may play in organizing receptor-initiated signaling pathways in the cardiovascular system and other tissues.
Key Words: GPCR • adrenergic • heptahelical • arrestin • phosphorylation
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|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
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|
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|
|
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|
|
|
|
|
|
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|
|