New roles for beta-arrestins in cell signaling: not just for seven-transmembrane receptors.
beta-arrestins, originally discovered as molecules that bind to and desensitize the activated and phosphorylated form of the G protein-coupled beta2-adrenergic receptor (beta2-AR), have recently emerged as multifunctional adaptor/scaffold proteins that dynamically assemble a wide range of multiprotein complexes in response to stimulation of most seven-transmembrane receptors (7TMRs). These complexes mediate receptor signaling, trafficking, and degradation. Moreover, beta-arrestins are increasingly found to perform analogous functions for receptors from structurally diverse classes, including atypical 7TMRs such as frizzled and smoothened, the nicotinic cholinergic receptors, receptor tyrosine kinases, and cytokine receptors, thereby regulating a growing list of cellular processes such as chemotaxis, apoptosis, and metastasis.
Lefkowitz
Robert J
RJ
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710; Department of Biochemistry, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710. Electronic address: lefko001@mc.duke.edu.
Rajagopal
Keshava
K
Department of Surgery, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
Whalen
Erin J
EJ
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710.
D000818:Animals; D019390:Arrestins / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins
D019390:Arrestins; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; C450520:seven-transmembrane G-protein-coupled receptor