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2014 ; 67
(ä): 2.10.1-2.10.9
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Overview of different mechanisms of arrestin-mediated signaling
#MMPMID25446289
Gurevich VV
; Gurevich EV
Curr Protoc Pharmacol
2014[Dec]; 67
(ä): 2.10.1-2.10.9
PMID25446289
show ga
Arrestins are characterized by their ability to selectively bind active,
phosphorylated GPCRs and suppress (arrest) receptor coupling to G proteins.
Nonvisual arrestins are also signaling proteins in their own right, activating a
variety of cellular pathways. Arrestins are highly flexible proteins that can
assume many distinct conformations. In their receptor-bound conformation,
arrestins have higher affinity for a subset of partners. This explains how
receptor activation regulates certain branches of arrestin-dependent signaling
via arrestin recruitment to GPCRs. However, free arrestins are also active
molecular entities that act in other pathways and localize signaling proteins to
particular subcellular compartments, such as cytoskeleton. These functions are
regulated by the enhancement or reduction of arrestin affinity for target
proteins by other binding partners and by proteolytic cleavage. Recent findings
suggest that the two visual arrestins, arrestin-1 and arrestin-4, which are
expressed in photoreceptor cells, do not regulate signaling solely via binding to
photopigments but also interact with a variety of nonreceptor partners,
critically affecting the health and survival of photoreceptor cells. Detailed in
this overview are GPCR-dependent and independent modes of arrestin-mediated
regulation of cellular signaling pathways.