Referenced in: none

Automatically associated channels: Kir2.3

Title: Turning G proteins on and off using peptide ligands.

Authors: William W Ja, Ofer Wiser, Ryan J Austin, Lily Y Jan, Richard W Roberts

Journal, date & volume: ACS Chem. Biol., 2006 Oct 24 , 1, 570-4

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17168552

Abstract
Intracellular Galpha subunits represent potential therapeutic targets for a number of diseases. Here we describe three classes of new molecules that modulate G protein signaling by direct targeting of Galpha. Using messenger RNA display, we have identified unique peptide sequences that bind Galpha i1 . Functionally, individual peptides were found that either enhance or repress basal levels of G protein-activated inwardly rectifying potassium (GIRK) channel signaling, a downstream effector of G protein activation, indicating that the peptides directly turn G proteins on or off in vivo . A third functional class acts as a signaling attenuator; basal GIRK channel activity is unaffected but responses to repeated G protein activation are reduced. These data demonstrate that G protein-directed ligands can achieve physiological effects similar to those resulting from classical receptor targeting and may serve as leads for developing new classes of therapeutics.