Journal of Cell Science 115, e301-e301 (2002)
© 2002 The Company of Biologists Limited
ß-arrestins: terminators and scaffolds for GPCR signalling (p. 455)
ß-arrestins are a family of adapter proteins that bind to activated
G-protein-coupled receptors (GPCRs). Binding of these adapters is known to be
important for termination of G-protein activation, but recent work indicates
that it also allows GPCRs to stimulate additional signalling pathways. Louis
Luttrell and Robert Lefkowitz discuss the signal-terminating functions of
ß-arrestins as well as the novel signalling functions of these adapters.
The proteins are able to terminate GPCR signalling through three distinct
mechanisms: desensitization (steric inhibition of G protein activation);
sequestration (promotion of receptor endocytosis); and downregulation (sorting
of receptors for degradation). Their signalling function rests on their
ability to function as scaffolds: ß-arrestins can interact with a variety
of signalling molecules, including Src kinases and members of the ERK and JNK
MAP-kinase cascades. ß-arrestin-dependent activation of Src, for example,
is implicated in stimulation of neutrophil degranulation by the chemokine
receptor CXCR1. Given such scaffold functions, a key role of ß-arrestins
might be to modulate the spatial distribution of signalling modules controlled
by GPCRs.
Related articles in JCS:
- The role of ß-arrestins in the termination and transduction of G-protein-coupled receptor signals
- Louis M. Luttrell and Robert J. Lefkowitz
JCS 2002 115: 455-465.
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