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Science 26 February 1999:
Vol. 283. no. 5406, pp. 1328 - 1331
DOI: 10.1126/science.283.5406.1328
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Reports

Facilitation of Signal Onset and Termination by Adenylyl Cyclase

Klaus Scholich, 1 Jason B. Mullenix, 1 Claus Wittpoth, 1 Helen M. Poppleton, 1 Sandra C. Pierre, 1 Margaret A. Lindorfer, 2 James C. Garrison, 2 Tarun B. Patel 1*

The alpha  subunit (Gsalpha ) of the stimulatory heterotrimeric guanosine triphosphate binding protein (G protein) Gs activates all isoforms of mammalian adenylyl cyclase. Adenylyl cyclase (Type V) and its subdomains, which interact with Gsalpha , promoted inactivation of the G protein by increasing its guanosine triphosphatase (GTPase) activity. Adenylyl cyclase and its subdomains also augmented the receptor-mediated activation of heterotrimeric Gs and thereby facilitated the rapid onset of signaling. These findings demonstrate that adenylyl cyclase functions as a GTPase activating protein (GAP) for the monomeric Gsalpha and enhances the GTP/GDP exchange factor (GEF) activity of receptors.

1 Department of Pharmacology, University of Tennessee, Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA.
2 Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
*   To whom correspondence should be addressed. E-mail: tpatel{at}physio1.utmem.edu

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