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.
