Frizzled receptors signal through G proteins |
| |
Authors: | Andrea S Nichols Desiree H Floyd Stephen P Bruinsma Kirk Narzinski Thomas J Baranski |
| |
Institution: | 1. Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA;2. Department of Developmental Biology, Washington University School of Medicine, 660 South Euclid Ave., St. Louis, MO 63110, USA |
| |
Abstract: | Frizzled receptors have long been thought to couple to G proteins but biochemical evidence supporting such an interaction has been lacking. Here we expressed mammalian Wnt-Frizzled fusion proteins in Saccharomyces cerevisiae and tested the receptors' ability to activate the yeast mitogen-activated protein kinase (MAPK) pathway via heterotrimeric G proteins. Our results show that Frizzled receptors can interact with Gαi, Gαq, and Gαs proteins, thus confirming that Frizzled functions as a G protein coupled receptor (GPCR). However, the activity level of Frizzled-mediated G protein signaling was much lower than that of a typical GPCR and, surprisingly, was highest when coupled to Gαs. The Frizzled/Gαs interaction was further established in vivo as Drosophila expressing a loss-of-function Gαs allele rescued the photoreceptor differentiation phenotype of Frizzled mutant flies. Together, these data point to an important role for Frizzled as a nontraditional GPCR that preferentially couples to Gαs heterotrimeric G proteins. |
| |
Keywords: | |
本文献已被 ScienceDirect 等数据库收录! |
|