Can a GDP-liganded G-protein be active?

The replacement of GDP bound to the alpha-subunit of a G-protein by GTP is generally considered a crucial step in the activation of effectors by a G-protein. New data by Uğur et al. (2005) (p. 720) raise the possibility that for the heterotrimeric G-protein Gs, GDP-liganded Gs is able to activate the effector adenylyl cyclase as potently and effectively as when Gs is in its GTP bound form. We summarize here the evidence that GTP is necessary for effector activation by G-proteins and discuss potential implications and limitations of data to the contrary.