کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1964422 | 1058547 | 2013 | 8 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Frizzled receptors signal through G proteins Frizzled receptors signal through G proteins](/preview/png/1964422.png)
• Frizzled receptors interact with Gαi, Gαq, and Gαs proteins.
• Gαs-mediated Frizzled signaling regulates Drosophila eye development.
• Frizzled receptors might act as partial GEFs or functional GDIs.
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.
Journal: Cellular Signalling - Volume 25, Issue 6, June 2013, Pages 1468–1475