AC2 (adenylate cyclase 2) is stimulated by activation of Gq-coupled muscarinic receptors through PKC (protein kinase C) to generate localized cAMP in HEK (human embryonic kidney)-293 cells. In the present study, we utilized a sensitive live-cell imaging technique to unravel the proteins that play essential roles in a Gq-coupled muscarinic receptor-mediated cAMP signalling complex. We reveal that, upon agonist binding to the Gq-coupled muscarinic receptor, AKAP79 (A-kinase-anchoring protein 79) recruits PKC to activate AC2 to produce cAMP. The cAMP formed is degraded by PDE4 (phosphodiesterase 4) activated by an AKAP-anchored PKA (protein kinase A). Calcineurin, a phosphatase bound to AKAP79, is not involved in this regulation. Overall, a transient cAMP increase is generated from AC2 by Gq-coupled muscarinic receptor activation, subject to sophisticated regulation through AKAP79, PKC, PDE4 and PKA, which significantly enhances acetylcholine-mediated signalling.
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Research Article|
September 13 2013
AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex
Jia X. Shen;
Jia X. Shen
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Dermot M. F. Cooper
Dermot M. F. Cooper
1
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be addressed (email dmfc2@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
March 08 2013
Revision Received:
July 25 2013
Accepted:
July 29 2013
Accepted Manuscript online:
July 29 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 455 (1): 47–56.
Article history
Received:
March 08 2013
Revision Received:
July 25 2013
Accepted:
July 29 2013
Accepted Manuscript online:
July 29 2013
Citation
Jia X. Shen, Dermot M. F. Cooper; AKAP79, PKC, PKA and PDE4 participate in a Gq-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex. Biochem J 1 October 2013; 455 (1): 47–56. doi: https://doi.org/10.1042/BJ20130359
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