| First Author | Wang Q | Year | 2004 |
| Journal | Science | Volume | 304 |
| Issue | 5679 | Pages | 1940-4 |
| PubMed ID | 15218143 | Mgi Jnum | J:105642 |
| Mgi Id | MGI:3616148 | Doi | 10.1126/science.1098274 |
| Citation | Wang Q, et al. (2004) Spinophilin blocks arrestin actions in vitro and in vivo at G protein-coupled receptors. Science 304(5679):1940-4 |
| abstractText | 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. |
