Nama : Sintia
Widyo Wati
NPM : 2A214304
Kelas : 3EB24
The
Diverse Roles of Arrestin Scaffolds in G Protein–Coupled Receptor Signaling
Yuri
K. Peterson and Louis M. Luttrell
Martin
C. Michel, ASSOCIATE EDITOR
Pharmacological Reviews July 2017, 69 (3) 256-297;
DOI: https://doi.org/10.1124/pr.116.013367
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Abstract
The
visual/β-arrestins, a small family of proteins originally described for their
role in the desensitization and intracellular trafficking of G protein–coupled
receptors (GPCRs), have emerged as key regulators of multiple signaling
pathways. Evolutionarily related to a larger group of regulatory scaffolds that
share a common arrestin fold, the visual/β-arrestins acquired the capacity to
detect and bind activated GPCRs on the plasma membrane, which enables them to
control GPCR desensitization, internalization, and intracellular trafficking.
By acting as scaffolds that bind key pathway intermediates, visual/β-arrestins
both influence the tonic level of pathway activity in cells and, in some cases,
serve as ligand-regulated scaffolds for GPCR-mediated signaling. Growing
evidence supports the physiologic and pathophysiologic roles of arrestins and
underscores their potential as therapeutic targets. Circumventing
arrestin-dependent GPCR desensitization may alleviate the problem of
tachyphylaxis to drugs that target GPCRs, and find application in the
management of chronic pain, asthma, and psychiatric illness. As signaling
scaffolds, arrestins are also central regulators of pathways controlling cell
growth, migration, and survival, suggesting that manipulating their scaffolding
functions may be beneficial in inflammatory diseases, fibrosis, and cancer. In
this review we examine the structure–function relationships that enable
arrestins to perform their diverse roles, addressing arrestin structure at the
molecular level, the relationship between arrestin conformation and function,
and sites of interaction between arrestins, GPCRs, and nonreceptor-binding
partners. We conclude with a discussion of arrestins as therapeutic targets and
the settings in which manipulating arrestin function might be of clinical
benefit.
Footnotes
This
work was supported by National Institutes of Health [Grants R01 DK055524 (to
L.M.L.) and R01 GM095497 (to L.M.L.)], Department of Veterans Affairs Merit
Review Grant I01 BX003188 (to L.M.L.), and the Research Service of the
Charleston, South Carolina, Veterans Affairs Medical Center. The contents of
this article do not represent the views of the Department of Veterans Affairs
or the United States Government.
sumber: http://pharmrev.aspetjournals.org/content/69/3/256
