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Isoforms of Mammalian Adenylyl Cyclase: Multiplicities of Signaling
Table 1.
Regulatory Properties of Mammalian Adenylyl Cyclase Isoforms
| AC Isoforma,b | Chromosomal Location | Tissue Distribution | Regulation by G Protein Subunits | Protein Kinases | Calcium Effects | Putative Function |
|---|---|---|---|---|---|---|
| BAT, brown adipose tissue; LTP, long-term potentiation. | ||||||
| a All isoforms except sAC are inhibited by P-site inhibitors. | ||||||
| b Forskolin stimulates human AC1-AC8, whereas AC9 is weakly stimulated by forskolin. sAC is not affected by forskolin. | ||||||
| c Cited reference numbers. | ||||||
| d Gβγ stimulation of AC isoforms is conditional upon Gαs co-activation. | ||||||
| e Inhibition determined by transfection only and could be an indirect Gβγ effect. | ||||||
| f Denotes Gαi family members Gαi1, Gαi2, Gαi3, and Gαz. | ||||||
| g Inhibited by calcineurin. | ||||||
| h Stimulated by bicarbonate. | ||||||
| AC1 | 7p12 (154)c | Brain adrenal medulla | Stimulated by Gαs Inhibited by Gβγ Inhibited by Gαo | PKC: weak stimulation CaMKIV: inhibition | Stimulated by Ca2+-CaM inhibition | Learning, memory, LTP Synaptic plasticity |
| AC2 | 5p15 (155, 156) | Brain, skeletal muscle, lung, heart | Stimulated by Gαs Stimulated by Gβγd | PKC: stimulation | ||
| AC3 | 2p22-p24 (157) | Brain, olfactory epithelium | Stimulation by Gαs | PKC: weak stimulation CaMKII: inhibition | Stimulated by Ca2+-CaM | Olfaction |
| AC4 | 14q11.2 (156) | Brain heart, kidney, liver, lung, BAT, uterus | Stimulation by Gαs Stimulated by Gβγd | PKC: inhibition | ||
| AC5 | 3q13.2-q21 (157) | Heart, brain, kidney, liver, lung, uterus, adrenal, BAT | Stimulation by Gαs Inhibited by Gβγe Inhibited by Gαif | PKA: inhibition PKCα,ζ: stimulation | Inhibited | |
| AC6 | 12q12-q13 (157) | Ubiquitous | Stimulation by Gαs Inhibited by Gβγe Inhibited by Gαif | PKA: inhibition PKC: inhibition | Inhibited | |
| AC7 | 16q12-q13 (158) | Ubiquitous, highly expressed in brain | Stimulation by Gαs Stimulated by Gβγd | PKC: stimulation | Drug dependency | |
| AC8 | 8q24 (155, 156) | Brain, lung (testis, adrenal, uterus, heart) | Stimulation by Gαs | Stimulated byCa2+-CaM | Learning, memory, LTP, Synaptic plasticity | |
| AC9g | 16p13.3 (159) | Brain, skeletal muscle | Stimulation by Gαs | |||
| SACh | 1q24 (24) | Testis | Not regulated by G protein subunits | Sperm capacitation | ||
