Class III adenylate cyclases (ACs) are widespread signaling proteins, which translate diverse intracellular and extracellular stimuli into a uniform intracellular signal. They are typically composed of an N-terminal array of input domains and transducers, followed C-terminally by a catalytic domain, which, as a dimer, generates the second messenger cAMP. The input domains, which receive stimuli, and the transducers, which propagate the signals, are often found in other signaling proteins. The nature of stimuli and the regulatory mechanisms of ACs have been studied experimentally in only a few cases, and even in these, important questions remain open, such as whether eukaryotic ACs regulated by G protein-coupled receptors can also receive stimuli through their own membrane domains. Here we survey the current knowledge on regulation and intramolecular signal propagation in ACs and draw comparisons to other signaling proteins. We highlight the pivotal role of a recently identified cyclase-specific transducer element located N-terminally of many AC catalytic domains, suggesting an intramolecular signaling capacity.

III类腺苷酸环化酶（AC）是广泛使用的信号蛋白，可将多种细胞内和细胞外刺激物转化为均匀的细胞内信号。它们通常由输入域和换能器的N端阵列组成，然后C端是催化域，该催化域作为二聚体生成第二个信使cAMP。接收刺激的输入域和传播信号的传感器通常在其他信号蛋白中发现。刺激的性质和AC的调节机制仅在少数情况下进行了实验研究，即使在这些情况下，仍然存在重要的问题，例如受G蛋白偶联受体调控的真核AC是否也可以通过其自身的膜接受刺激域。在这里，我们调查有关AC中的调节和分子内信号传播的当前知识，并与其他信号蛋白进行比较。我们强调了最近确定的位于许多AC催化域的N末端的环化酶特异性换能器元件的关键作用，表明分子内信号传导能力。