title: β-Arrestin-kinase scaffolds: turn them on or turn them off?
abstract: G-protein-coupled receptors (GPCRs) can signal through heterotrimeric G-proteins or through β-arrestins to elicit responses to a plethora of extracellular stimuli. While the mechanisms underlying G-protein signaling is relatively well understood, the mechanisms by which β-arrestins regulate the diverse set of proteins with which they associate remain unclear. Multi-protein complexes are a common feature of β-arrestin-dependent signaling. The first two such complexes discovered were the mitogen-activated kinases modules associated with extracellular regulated kinases (ERK1/2) and Jnk3. Subsequently a number of other kinases have been shown to undergo β-arrestin-dependent regulation, including Akt, phosphatidylinositol-3kinase (PI3K), Lim-domain-containing kinase (LIMK), calcium calmodulin kinase II (CAMKII), and calcium calmodulin kinase kinase β (CAMKKβ). Some are positively and some negatively regulated by β-arrestin association. One of the missing links to understanding these pathways is the molecular mechanisms by which the activity of these kinases is regulated. Do β-arrestins merely serve as scaffolds to bring enzyme and substrate together or do they have a direct effect on the enzymatic activities of target kinases? Recent evidence suggests that both mechanisms are involved and that the mechanisms by which β-arrestins regulate kinase activity varies with the target kinase. This review discusses recent advances in the field focusing on 5 kinases for which considerable mechanistic detail and specific sites of interaction have been elucidated.
authors: Department of Biomedical Sciences, University of California Riverside, Riverside, CA, USA.
authors: Alice
authors: A
authors: Lin
authors: Kathryn A
authors: KA
authors: DeFea
mesh_terms: D019390:Arrestins / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D000071557:beta-Arrestins; D017346:Protein Serine-Threonine Kinases