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Molecular Pharmacology Fast Forward
First published on June 24, 2005; DOI: 10.1124/mol.105.016071


0026-895X/05/6803-559-562$20.00
Mol Pharmacol 68:559-562, 2005

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Perspective

Can a GDP-Liganded G-Protein Be Active?

Thomas Wieland, and Martin C. Michel

Department of Pharmacology and Toxicology, University of Heidelberg, Mannheim, Germany (T.W.); and Department of Pharmacology and Pharmacotherapy, University of Amsterdam, Amsterdam, The Netherlands (M.C.M.)

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 Ugur 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.


Received June 23, 2005; accepted June 24, 2005

Address correspondence to: Prof. Martin C. Michel, Dept. Pharmacol. and Pharmacother., Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands, E-mail: m.c.michel{at}amc.uva.nl







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