| First Author | Wang J | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1706 |
| PubMed ID | 29167435 | Mgi Jnum | J:257217 |
| Mgi Id | MGI:6105990 | Doi | 10.1038/s41467-017-01855-z |
| Citation | Wang J, et al. (2017) Galphai is required for carvedilol-induced beta1 adrenergic receptor beta-arrestin biased signaling. Nat Commun 8(1):1706 |
| abstractText | The beta1 adrenergic receptor (beta1AR) is recognized as a classical Galphas-coupled receptor. Agonist binding not only initiates G protein-mediated signaling but also signaling through the multifunctional adapter protein beta-arrestin. Some betaAR ligands, such as carvedilol, stimulate betaAR signaling preferentially through beta-arrestin, a concept known as beta-arrestin-biased agonism. Here, we identify a signaling mechanism, unlike that previously known for any Galphas-coupled receptor, whereby carvedilol induces the transition of the beta1AR from a classical Galphas-coupled receptor to a Galphai-coupled receptor stabilizing a distinct receptor conformation to initiate beta-arrestin-mediated signaling. Recruitment of Galphai is not induced by any other betaAR ligand screened, nor is it required for beta-arrestin-bias activated by the beta2AR subtype of the betaAR family. Our findings demonstrate a previously unrecognized role for Galphai in beta1AR signaling and suggest that the concept of beta-arrestin-bias may need to be refined to incorporate the selective bias of receptors towards distinct G protein subtypes. |
