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Stimulation of Mammalian G-protein-responsive Adenylyl Cyclases by Carbon Dioxide

Townsend, PD; Holliday, PM; Fenyk, S; Hess, KC; Gray, MA; Hodgson, DRW; Cann, MJ

Stimulation of Mammalian G-protein-responsive Adenylyl Cyclases by Carbon Dioxide Thumbnail


PD Townsend

PM Holliday

S Fenyk

KC Hess

MA Gray


Carbon dioxide is fundamental to the physiology of all organisms. There is considerable interest in the precise molecular mechanisms that organisms use to directly sense CO2. Here we demonstrate that a mammalian recombinant G-protein-activated adenylyl cyclase and the related Rv1625c adenylyl cyclase of Mycobacterium tuberculosis are specifically stimulated by CO2. Stimulation occurred at physiological concentrations of CO2 through increased kcat. CO2 increased the affinity of enzyme for metal co-factor, but contact with metal was not necessary as CO2 interacted directly with apoenzyme. CO2 stimulated the activity of both G-protein-regulated adenylyl cyclases and Rv1625c in vivo. Activation of G-protein regulated adenylyl cyclases by CO2 gave a corresponding increase in cAMP-response element-binding protein (CREB) phosphorylation. Comparison of the responses of the G-protein regulated adenylyl cyclases and the molecularly, and biochemically distinct mammalian soluble adenylyl cyclase revealed that whereas G-protein-regulated enzymes are responsive to CO2, the soluble adenylyl cyclase is responsive to both CO2 and bicarbonate ion. We have, thus, identified a signaling enzyme by which eukaryotes can directly detect and respond to fluctuating CO2.


Townsend, P., Holliday, P., Fenyk, S., Hess, K., Gray, M., Hodgson, D., & Cann, M. (2009). Stimulation of Mammalian G-protein-responsive Adenylyl Cyclases by Carbon Dioxide. Journal of Biological Chemistry, 284(2), 784-791.

Journal Article Type Article
Publication Date Jan 1, 2009
Deposit Date Sep 29, 2011
Publicly Available Date Oct 13, 2011
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 284
Issue 2
Pages 784-791
Keywords Mycobacterium-Tuberculosis, Intracellular PH, Camp production, Nucleotide phosphodiesterase, Caenorhabditis-elegans, Escherichia-coli, CO2, Bicarbonate, Expression, Cells.
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Published Journal Article (567 Kb)

Copyright Statement
This research was originally published in Journal of biological chemistry. Townsend, P.D. and Holliday, P.M. and Fenyk, S. and Hess, K.C. and Gray, M.A. and Hodgson, D.R.W. and Cann, M.J. Stimulation of mammalian G-protein-responsive adenylyl cyclases by carbon dioxide. 2008; 284:784-791. © the American Society for Biochemistry and Molecular Biology.

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