Isoforms of Mammalian Adenylyl Cyclase: Multiplicities of Signaling

Multiple modes of regulation of adenylyl cyclase isoforms. (A) The pattern of regulation of AC1 as illustrated is representative also for AC3 and AC8. R1 represents a G protein–coupled receptor, such as the glucagon or β2-adrenergic receptor, that couples to the stimulatory G protein Gα_s. R2 represents a G protein–coupled receptor, such as the muscarinic M2 or α1-adrenergic receptor, that couples to the inhibitory G protein Gα_i. (B) The pattern of regulation of AC2 as illustrated is representative of the regulation of AC4 and AC7. Note that Gβγ regulation of AC2 is dependent on Gα_s co-activation and does not activate AC by itself. PKC can use AC as a substrate, resulting in elevation of basal activity and inhibition of the Gβγ superactivation. (C) The pattern of regulation of AC5 is representative also of AC6. (PKA, protein kinase A; PKC, protein kinase C; CaM, calmodulin; CaMK, calmodulin-dependent kinase; NO, nitric oxide; VDCC, voltage-dependent Ca²⁺ channel.)