Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 26 February 1999:
Vol. 283. no. 5406, pp. 1328 - 1331
DOI: 10.1126/science.283.5406.1328
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
N Terminus of Type 5 Adenylyl Cyclase Scaffolds Gs Heterotrimer.
R. Sadana, N. Dascal, and C. W. Dessauer (2009)
Mol. Pharmacol. 76, 1256-1264
   Abstract »    Full Text »    PDF »
Physiological functions of the imprinted Gnas locus and its protein variants G{alpha}s and XL{alpha}s in human and mouse.
A. Plagge, G. Kelsey, and E. L Germain-Lee (2008)
J. Endocrinol. 196, 193-214
   Abstract »    Full Text »    PDF »
Mammalian G Proteins and Their Cell Type Specific Functions.
N. Wettschureck and S. Offermanns (2005)
Physiol Rev 85, 1159-1204
   Abstract »    Full Text »    PDF »
Minireview: GNAS: Normal and Abnormal Functions.
L. S. Weinstein, J. Liu, A. Sakamoto, T. Xie, and M. Chen (2004)
Endocrinology 145, 5459-5464
   Abstract »    Full Text »    PDF »
Insights into G Protein Structure, Function, and Regulation.
T. M. Cabrera-Vera, J. Vanhauwe, T. O. Thomas, M. Medkova, A. Preininger, M. R. Mazzoni, and H. E. Hamm (2003)
Endocr. Rev. 24, 765-781
   Abstract »    Full Text »    PDF »
RGS6, RGS7, RGS9, and RGS11 Stimulate GTPase Activity of Gi Family G-proteins with Differential Selectivity and Maximal Activity.
S. B. Hooks, G. L. Waldo, J. Corbitt, E. T. Bodor, A. M. Krumins, and T. K. Harden (2003)
J. Biol. Chem. 278, 10087-10093
   Abstract »    Full Text »    PDF »
Isoforms of Mammalian Adenylyl Cyclase: Multiplicities of Signaling.
R. K. Sunahara and R. Taussig (2002)
Mol. Interv. 2, 168-184
   Abstract »    Full Text »    PDF »
Dopamine D2 Receptor-Induced Heterologous Sensitization of Adenylyl Cyclase Requires Galpha s: Characterization of Galpha s-Insensitive Mutants of Adenylyl Cyclase V.
V. J. Watts, R. Taussig, R. L. Neve, and K. A. Neve (2001)
Mol. Pharmacol. 60, 1168-1172
   Abstract »    Full Text »    PDF »
ACh-induced rebound stimulation of L-type Ca2+ current in guinea-pig ventricular myocytes, mediated by G{beta}{gamma}-dependent activation of adenylyl cyclase.
A. E Belevych, C. Sims, and R. D Harvey (2001)
J. Physiol. 536, 677-692
   Abstract »    Full Text »    PDF »
Endocrine Manifestations of Stimulatory G Protein {alpha}-Subunit Mutations and the Role of Genomic Imprinting.
L. S. Weinstein, S. Yu, D. R. Warner, and J. Liu (2001)
Endocr. Rev. 22, 675-705
   Abstract »    Full Text »    PDF »
Stoichiometry and Compartmentation in G Protein-Coupled Receptor Signaling: Implications for Therapeutic Interventions Involving Gs.
R. S. Ostrom, S. R. Post, and P. A. Insel (2000)
J. Pharmacol. Exp. Ther. 294, 407-412
   Abstract »    Full Text »
The Molecular Basis for Distinct {beta}-Adrenergic Receptor Subtype Actions in Cardiomyocytes.
S. F. Steinberg (1999)
Circ. Res. 85, 1101-1111
   Full Text »    PDF »
Rapid GTP binding and hydrolysis by Gq promoted by receptor and GTPase-activating proteins.
S. Mukhopadhyay and E. M. Ross (1999)
PNAS 96, 9539-9544
   Abstract »    Full Text »    PDF »
Adenylyl Cyclase Regulates Signal Onset via the Inhibitory GTP-binding Protein, Gi.
C. Wittpoth, K. Scholich, J. D. Bilyeu, and T. B. Patel (2000)
J. Biol. Chem. 275, 25915-25919
   Abstract »    Full Text »    PDF »
Phospholipase Cdelta 1 Is a Guanine Nucleotide Exchanging Factor for Transglutaminase II (Galpha h) and Promotes alpha 1B-Adrenoreceptor-mediated GTP Binding and Intracellular Calcium Release.
K. J. Baek, S. K. Kang, D. S. Damron, and M.-J. Im (2001)
J. Biol. Chem. 276, 5591-5597
   Abstract »    Full Text »    PDF »
The Regulation of Type 7 Adenylyl Cyclase by Its C1b Region and Escherichia coli Peptidylprolyl Isomerase, SlyD.
S.-Z. Yan, J. A. Beeler, Y. Chen, R. K. Shelton, and W.-J. Tang (2001)
J. Biol. Chem. 276, 8500-8506
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)