Beta-arrestins and cell signaling.
Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that beta-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the beta-arrestins bring elements of specific signaling pathways into close proximity. beta-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition, investigators are discovering new roles for beta-arrestins in nuclear functions. Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis.
DeWire
Scott M
SM
Howard Hughes Medical Institute and Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ahn
Seungkirl
S
Lefkowitz
Robert J
RJ
Shenoy
Sudha K
SK
D000818:Animals; D019390:Arrestins / Q000502:physiology* / Q000648:ultrastructure; D001711:Biotransformation / Q000502:physiology; D002467:Cell Nucleus / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D053612:Janus Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
D019390:Arrestins; D000071557:beta-Arrestins; D053612:Janus Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases