Sunahara R K, Dessauer C W, Gilman A G
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Annu Rev Pharmacol Toxicol. 1996;36:461-80. doi: 10.1146/annurev.pa.36.040196.002333.
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 alpha subunit of G alpha, a receptor-regulated, heterotrimeric guanine nucleotide-binding protein, and by the diterpene forskolin. Certain cyclases are also activated by Ca(2+)-calmodulin, while some are inhibited by the alpha subunits of the three Gi proteins. The discovery of new isoforms has also revealed unanticipated mechanisms of regulation, including activation or inhibition by the G-protein beta gamma subunit complex, inhibition by G(o) alpha, 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 enyzmes 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.
分子克隆技术已使人们能够鉴定出哺乳动物腺苷酸环化酶的几种新亚型；这些蛋白质目前构成了一个至少包含10种成员的家族。所有膜结合酶都可被Gα的α亚基激活，Gα是一种受受体调节的异源三聚体鸟嘌呤核苷酸结合蛋白，同时也可被二萜类化合物福斯可林激活。某些环化酶还可被Ca(2+)-钙调蛋白激活，而有些则被三种Gi蛋白的α亚基抑制。新亚型的发现还揭示了一些意想不到的调节机制，包括被G蛋白βγ亚基复合物激活或抑制、被G(o)α抑制、被Ca2+抑制以及被蛋白激酶C和A磷酸化。激活剂的作用往往具有高度协同性或条件性，这表明这些酶具有作为巧合探测器的功能。大量的受体、G蛋白和腺苷酸环化酶使得能够组装出具有多种整合特性的非常复杂的信号系统。
