Journal
BIOCHEMICAL JOURNAL
Volume 455, Issue -, Pages 47-56Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130359
Keywords
adenylate cyclase 2 (AC2); A-kinase-anchoring protein 79 (AKAP79); muscarinic receptor; phosphodiesterase 4 (PDE4); protein kinase A (PKA); protein kinase C (PKC)
Categories
Funding
- Wellcome Trust [RG 31760]
- Newton Trust
Ask authors/readers for more resources
AC2 (adenylate cyclase 2) is stimulated by activation of G(q)-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 G(q)-coupled muscarinic receptor-mediated cAMP signalling complex. We reveal that, upon agonist binding to the G.-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 G(q)-coupled muscarinic receptor activation, subject to sophisticated regulation through AKAP79, PKC, PDE4 and PKA, which significantly enhances acetylcholine-mediated signalling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available