AKAP79 and PKC, PKA and PDE4, participate in a Gq-linked muscarinic receptor and adenylyl cyclase 2 cAMP signalling complex

Adenylyl cyclase (AC) 2 is stimulated by activation of Gq-coupled muscarinic receptors through PKC to generate localised cAMP in HEK-293 cells [1-3]. In the current study, we utilise 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 recruits PKC to activate AC2 to produce cAMP. The cAMP formed is degraded by PDE4 activated by an AKAP anchored-PKA. 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.

Source: BJ Cell - July 29, 2013 Category: Biochemistry Authors: J X. Shen, D M.F. Cooper Tags: BJ Signal Source Type: research