Abstract

The replacement of GDP bound to the α-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 G_s, GDP-liganded G_s is able to activate the effector adenylyl cyclase as potently and effectively as when G_s 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.