AKAP79, PKC, PKA and PDE4 participate in a G(q)-linked muscarinic receptor and adenylate cyclase 2 cAMP signalling complex

作者：Shen Jia X; Cooper Dermot M F^*

来源：Biochemical Journal, 2013, 455(1): 47-56.

DOI：10.1042/BJ20130359

• adenylate cyclase 2 (AC2)
• A-kinase-anchoring protein 79 (AKAP79)
• muscarinic receptor
• phosphodiesterase 4 (PDE4)
• protein kinase A (PKA)
• protein kinase C (PKC)

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.

• 出版日期2013-10-1