Abstract
The heterotrimeric G proteins are known to have a variety of downstream effectors, but G(s) was long thought to be specifically coupled to adenylyl cyclases. A new study indicates that activated G(s) can also directly interact with a guanine nucleotide exchange factor for Rho family small GTPases, PDZ-RhoGEF. This novel interaction mediates activation of the small G protein Cdc42 by G(s)-coupled GPCRs, inducing cytoskeletal rearrangements and formation of filopodia-like structures. Furthermore, overexpression of a minimal PDZ-RhoGEF fragment can down-regulate cAMP signaling, suggesting that this effector competes with canonical signaling. This first demonstration that the Gα(s) subfamily regulates activity of Rho GTPases extends our understanding of Gα(s) activity and establishes RhoGEF coupling as a universal Gα function.