STIMULATION OF THE TYPE-III OLFACTORY ADENYLYL CYCLASE BY CALCIUM AND CALMODULIN

STIMULATION OF THE TYPE-III OLFACTORY ADENYLYL CYCLASE BY CALCIUM AND CALMODULIN
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DOI:
10.1021/bi00143a019
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发表时间:
1992-07-21
期刊:
影响因子:
2.9
通讯作者:
STORM, DR
STORM, DR
中科院分区:
生物学3区
文献类型:
--
作者:
CHOI, EJ;XIA, ZG;STORM, DR

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腺苷酸环化酶的表征已经通过分离包括I型和III型酶的不同腺苷酸环化酶的cDNA克隆而得到促进。I型腺苷酸环化酶活性在动物细胞中的表达已经确定该酶受钙调蛋白和Ca 2+的刺激。III型腺苷酸环化酶在嗅觉神经元中富集,并受刺激性G蛋白的调节。III型腺苷酸环化酶对Ca 2+和钙调素的敏感性尚未报道。在这项研究中,III型腺苷酸环化酶在人肾293细胞中表达,以确定该酶是否被Ca 2+和钙调素刺激。在没有其他效应物的情况下,III型酶不受Ca 2+和钙调素的刺激。然而,它是通过钙调蛋白时,酶被同时激活GppNHp或毛喉素钙2+刺激。I型和III型腺苷酸环化酶的半最大刺激的游离Ca 2+浓度分别为0.05和5.0 μ M Ca 2+。这些数据表明,III型腺苷酸环化酶是由钙刺激时,酶被激活的G-蛋白偶联受体和增加frec钙2+伴随受体激活可能会放大的主要环AMP信号。
Characterization of adenylyl cyclases has been facilitated by the isolation of cDNA clones for distinct adenylyl cyclases including the type I and type III enzymes. Expression of type I adenylyl cyclase activity in animal cells has established that this enzyme is stimulated by calmodulin and Ca2+. Type III adenylyl cyclase is enriched in olfactory neurons and is regulated by stimulatory G proteins. The sensitivity of the type III adenylyl cyclase to Ca2+ and calmodulin has not been reported. In this study, type III adenylyl cyclase was expressed in human kidney 293 cells to determine if the enzyme is stimulated by Ca2+ and calmodulin. The type III enzyme was not stimulated by Ca2+ and calmodulin in the absence of other effectors. It was, however, stimulated by Ca2+ through calmodulin when the enzyme was concomitantly activated by either GppNHp or forskolin. The concentrations of free Ca2+ for half-maximal stimulation of type I and type III adenylyl cyclases were 0.05 and 5.0-mu-M Ca2+, respectively. These data suggest that the type III adenylyl cyclase is stimulated by Ca2+ when the enzyme is activated by G-protein-coupled receptors and that increases in frec Ca2+ accompanying receptor activation may amplify the primary cyclic AMP signal.