Abstract
Molecular cloning has permitted identification of several novel isoforms of mammalian adenylyl cyclase; these proteins now comprise a family of at least 10. All of the membrane-bound enzymes are activated by the α subunit of G(α), a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. Certain cyclases are also activated by Ca2+-calmodulin, while some are inhibited by the α subunits of the three G(i) proteins. The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein βγ subunit complex, inhibition by G(0α), inhibition by Ca2+, and phosphorylation by protein kinases C and A. The effects of activators are often highly synergistic or conditional, suggesting function of these enzymes as coincidence detectors. The plethora of receptors, G proteins, and adenylyl cyclases permits assembly of very complex signaling systems with a wide variety of integrative characteristics.
Original language | English (US) |
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Pages (from-to) | 461-480 |
Number of pages | 20 |
Journal | Annual review of pharmacology and toxicology |
Volume | 36 |
DOIs | |
State | Published - 1996 |
Keywords
- G proteins
- adenylyl cyclase
- calmodulin
- forskolin
- phosphorylation
ASJC Scopus subject areas
- Toxicology
- Pharmacology