| First Author | Xu C | Year | 2010 |
| Journal | J Cell Sci | Volume | 123 |
| Issue | Pt 24 | Pages | 4259-70 |
| PubMed ID | 21098639 | Mgi Jnum | J:182901 |
| Mgi Id | MGI:5317063 | Doi | 10.1242/jcs.073742 |
| Citation | Xu C, et al. (2010) Serine 363 of the {delta}-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands. J Cell Sci 123(Pt 24):4259-70 |
| abstractText | Distinct opioid receptor agonists have been proved to induce differential patterns of ERK activation, but the underlying mechanisms remain unclear. Here, we report that Ser363 in the delta-opioid receptor (deltaOR) determines the different abilities of the deltaOR agonists DPDPE and TIPP to activate ERK by G-protein- or beta-arrestin-dependent pathways. Although both DPDPE and TIPP activated ERK1/2, they showed different temporal, spatial and desensitization patterns of ERK activation. We show that that DPDPE employed G protein as the primary mediator to activate the ERK cascade in an Src-dependent manner, whereas TIPP mainly adopted a beta-arrestin1/2-mediated pathway. Moreover, we found that DPDPE gained the capacity to adopt the beta-arrestin1/2-mediated pathway upon Ser363 mutation, accompanied by the same pattern of ERK activation as that induced by TIPP. Additionally, we found that TIPP- but not DPDPE-activated ERK could phosphorylate G-protein-coupled receptor kinase-2 and beta-arrestin1. However, such functional differences of ERK disappeared with the mutation of Ser363. Therefore, the present study reveals a crucial role for Ser363 in agonist-specific regulation of ERK activation patterns and functions. |
