| Title : G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14.Galphai1 complex in live cells - Vellano_2011_J.Biol.Chem_286_38659 |
| Author(s) : Vellano CP , Maher EM , Hepler JR , Blumer JB |
| Ref : Journal of Biological Chemistry , 286 :38659 , 2011 |
| Abstract : Regulator of G protein Signaling 14 (RGS14) is a multifunctional scaffolding protein that integrates both conventional and unconventional G protein signaling pathways. Like other RGS (regulator of G protein signaling) proteins, RGS14 acts as a GTPase accelerating protein to terminate conventional Galpha(i/o) signaling. However, unlike other RGS proteins, RGS14 also contains a G protein regulatory/GoLoco motif that specifically binds Galpha(i1/3)-GDP in cells and in vitro. The non-receptor guanine nucleotide exchange factor Ric-8A can bind and act on the RGS14.Galpha(i1)-GDP complex to play a role in unconventional G protein signaling independent of G protein-coupled receptors (GPCRs). Here we demonstrate that RGS14 forms a Galpha(i/o)-dependent complex with a G(i)-linked GPCR and that this complex is regulated by receptor agonist and Ric-8A (resistance to inhibitors of cholinesterase-8A). Using live cell bioluminescence resonance energy transfer, we show that RGS14 functionally associates with the alpha(2A)-adrenergic receptor (alpha(2A)-AR) in a Galpha(i/o)-dependent manner. This interaction is markedly disrupted after receptor stimulation by the specific agonist UK14304, suggesting complex dissociation or rearrangement. Agonist-mediated dissociation of the RGS14.alpha(2A)-AR complex occurs in the presence of Galpha(i/o) but not Galpha(s) or Galpha(q). Unexpectedly, RGS14 does not dissociate from Galpha(i1) in the presence of stimulated alpha(2A)-AR, suggesting preservation of RGS14.Galpha(i1) complexes after receptor activation. However, Ric-8A facilitates dissociation of both the RGS14.Galpha(i1) complex and the Galpha(i1)-dependent RGS14.alpha(2A)-AR complex after receptor activation. Together, these findings indicate that RGS14 can form complexes with GPCRs in cells that are dependent on Galpha(i/o) and that these RGS14.Galpha(i1).GPCR complexes may be substrates for other signaling partners such as Ric-8A. |
| ESTHER : Vellano_2011_J.Biol.Chem_286_38659 |
| PubMedSearch : Vellano_2011_J.Biol.Chem_286_38659 |
| PubMedID: 21880739 |
Vellano CP, Maher EM, Hepler JR, Blumer JB (2011)
G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14.Galphai1 complex in live cells
Journal of Biological Chemistry
286 :38659
Vellano CP, Maher EM, Hepler JR, Blumer JB (2011)
Journal of Biological Chemistry
286 :38659