Galphao/i-stimulated proteosomal degradation of RGS20: a mechanism for temporal integration of Gs and Gi pathways.

Journal Article (Journal Article)

The G(s) and G(i) pathways interact to control the levels of intracellular cAMP. Although coincident signaling through G(s) and G(i)-coupled receptors can attenuate G(s)-stimulated cAMP levels, it is not known if prior activation of the G(i) pathway can affect signaling by G(s)-coupled receptors. We have found that activated Galpha(o/i) interact with RGS20, a GTPase activating protein for members of the Galpha(omicron/i) family. Interaction between Galpha(o/i) and RGS20 results in decreased cellular levels of RGS20. This decrease was induced by activated Galpha(o) and Galpha(i2) but not by Galpha(q), Galpha(i1) or Galpha(i3.) The Galpha(o/i)-induced decrease in RGS20 can be blocked by proteasomal inhibitors lactacystin or MG132. Activated Galpha(o) stimulates the ubiquitination of RGS20. The serotonin-1A receptor that couples to G(o/i) reduces the levels of RGS20 and this effect is blocked by lactacystin, suggesting that G(o/i) promotes the degradation of RGS20. Expression of RGS20 attenuates the inhibition of beta-adrenergic receptor-induced cAMP levels mediated by the serotonin-1A receptor. Prior activation of the serotonin-1A receptor results in loss of the RGS20-mediated attenuation, and the loss of attenuation is blocked when lactacystin is included during the prior treatment. These observations suggest that G(o/i)-coupled receptors, by stimulating the degradation of RGS20, can regulate how subsequent activation of the G(s) and G(i) pathways controls cellular cAMP levels, thus allowing for signal integration.

Full Text

Duke Authors

Cited Authors

  • Pagano, M; Jordan, JD; Neves, SR; Nguyen, T; Iyengar, R

Published Date

  • June 2008

Published In

Volume / Issue

  • 20 / 6

Start / End Page

  • 1190 - 1197

PubMed ID

  • 18407463

Pubmed Central ID

  • PMC3107604

International Standard Serial Number (ISSN)

  • 0898-6568

Digital Object Identifier (DOI)

  • 10.1016/j.cellsig.2008.02.008


  • eng

Conference Location

  • England