Molecular mechanisms of G protein-coupled receptor signaling: role of G protein-coupled receptor kinases and arrestins in receptor desensitization and resensitization.
Dynamic regulation of G protein-coupled receptor signaling demands a coordinated balance between mechanisms leading to the generation, turning off and re-establishment of agonist-mediated signals. G protein-coupled receptor kinases (GRKs) and arrestin proteins not only mediate agonist-dependent G protein-coupled receptor desensitization, but also initiate the internalization (sequestration) of activated receptors, a process leading to receptor resensitization. Studies on the specificity of beta-arrestin functions reveal a multiplicity of G protein-coupled receptor endocytic pathways and suggest that beta-arrestins might serve as adaptors specifically targeting receptors for dynamin-dependent clathrin-mediated endocytosis. Moreover, inactivation of the GRK2 gene in mice has lead to the discovery of an unexpected role of GRK2 in cardiac development, further emphasizing the pleiotropic function of GRKs and arrestins.
Zhang
J
J
Howard Hughes Medical Institute Laboratories, Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ferguson
S S
SS
Barak
L S
LS
Aber
M J
MJ
Giros
B
B
Lefkowitz
R J
RJ
Caron
M G
MG
D000818:Animals; D019393:Arrestin / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction
D019393:Arrestin; D011956:Receptors, Cell Surface; D020794:Receptor Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins