Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors.

Journal Article (Journal Article)

Arrestin regulates almost all G protein-coupled receptor (GPCR)-mediated signaling and trafficking. We report that the multidomain protein, spinophilin, antagonizes these multiple arrestin functions. Through blocking G protein receptor kinase 2 (GRK2) association with receptor-Gbetagamma complexes, spinophilin reduces arrestin-stabilized receptor phosphorylation, receptor endocytosis, and the acceleration of mitogen-activated protein kinase (MAPK) activity following endocytosis. Spinophilin knockout mice were more sensitive than wild-type mice to sedation elicited by stimulation of alpha2 adrenergic receptors, whereas arrestin 3 knockout mice were more resistant, indicating that the signal-promoting, rather than the signal-terminating, roles of arrestin are more important for certain response pathways. The reciprocal interactions of GPCRs with spinophilin and arrestin represent a regulatory mechanism for fine-tuning complex receptor-orchestrated cell signaling and responses.

Full Text

Duke Authors

Cited Authors

  • Wang, Q; Zhao, J; Brady, AE; Feng, J; Allen, PB; Lefkowitz, RJ; Greengard, P; Limbird, LE

Published Date

  • June 25, 2004

Published In

Volume / Issue

  • 304 / 5679

Start / End Page

  • 1940 - 1944

PubMed ID

  • 15218143

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.1098274


  • eng

Conference Location

  • United States