Frizzled receptors signal through G proteins.

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).

Beta2-chimaerin in cancer signaling: connecting cell adhesion and MAP kinase activation.

The chimaerins are Rac GTPase-activating proteins that bind diacylglycerol. Emerging evidence implicates beta2-chimaerin in tumor progression. Here, we discuss our recent work in Drosophila melanogaster in the context of previous studies performed in human cancer cell lines that together lend new mechanistic insight into the role of chimaerins in cancer.

Chimaerin and Rac regulate cell number, adherens junctions, and ERK MAP kinase signaling in the Drosophila eye.

The chimaerin family of Rac GTPase-activating proteins (GAPs) has been implicated in neural development and tumor progression, although the cellular mechanisms of their effects are poorly understood. To study their physiologic function, we used the Drosophila retina as a model system. Reduced expression of the fly chimaerin ortholog RhoGAP5a in the pupal eye led to an excess of interommatidial pigment cells, aberrant cell contacts, and an increase in activated ERK that localized specifically to the plasma membrane.

C5a receptor oligomerization. II. Fluorescence resonance energy transfer studies of a human G protein-coupled receptor expressed in yeast.

Recent studies demonstrate that members of the superfamily of G protein-coupled receptors (GPCRs) form oligomers both in vitro and in vivo. The mechanisms by which GPCRs oligomerize and the roles of accessory proteins in this process are not well understood. We used disulfide-trapping experiments to show that C5a receptors, expressed in mammalian cells, reside in membranes as oligomers (Klco, J.