Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade.
Increased expression of Gs(alpha) enhances activation of the adenylyl cyclase signal transduction cascade.
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DOI：
10.1210/mend.11.8.9957
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发表时间：
1997-07
影响因子：
--
通讯作者：
X. Yang;F. Lee;G. Wand
中科院分区：
文献类型：
--
作者：
X. Yang;F. Lee;G. Wand
刺激性G蛋白G（S）α的表达在人体组织和啮齿类动物中枢神经系统中可以在3倍范围内变化。事实上，与不酗酒的后代相比，酗酒者的后代在某些组织中有更高水平的G（S）α表达。本研究的目的是检验G（S）α表达水平与腺苷酸环化酶（AC）级联反应诱导之间存在因果关系的假设。该方法采用在诱导型金属硫蛋白启动子调控下用52-kDa形式的G（S）α的cDNA瞬时转染HEK 293细胞。将转染子暴露于不同浓度（0-125 μ M）的硫酸锌，其产生3倍范围的膜G（S）α表达。发现产生的G（S）α表达的范围模拟来自人组织和大鼠脑的膜中的G（S）α表达的生理相关谱。观察到G（S）α表达的诱导增加了组成型以及刺激的cAMP积累。此外，G（S）α表达的诱导增加了cAMP积累远端的事件，包括转录因子、cAMP反应元件结合蛋白的磷酸化和cAMP依赖性报告基因的转录激活。总之，这些研究表明，G（S）α表达的量对从膜到核的AC级联的活性水平具有显著影响。假设G（S）α表达不同的个体在某些cAMP依赖性基因的表达上也可能不同。
Expression of the stimulatory G protein, G(S)alpha, can vary over a 3-fold range in human tissues and in rodent central nervous system. In fact, the offspring of alcoholics have higher levels of G(S)alpha expression in certain tissues compared with the offspring of nonalcoholics. The aim of this research was to test the hypothesis that a causal relationship exists between the level of expression of G(S)alpha and induction of the adenylyl cyclase (AC) cascade. The methodology employed transient transfection of HEK 293 cells with a cDNA for the 52-kDa form of G(S)alpha under regulation by inducible metallothionein promoters. Transfectants were exposed to varying concentrations (0-125 microM) of zinc sulfate that produced a 3-fold range of membrane G(S)alpha expression. The range of G(S)alpha expression produced was found to mimic a physiologically relevant spectrum of G(S)alpha expression in membranes derived from human tissues and rat brain. It was observed that induction of G(S)alpha expression increased constitutive as well as stimulated cAMP accumulation. Moreover, induction of G(S)alpha expression increased events distal to the accumulation of cAMP including the phosphorylation of the transcription factor, cAMP response element binding protein and transcriptional activation of cAMP-dependent reporter genes. In summary, these studies show that the amount of G(S)alpha expression has a marked impact on the level of activity of the AC cascade from the membrane through to the nucleus. It is hypothesized that individuals who differ in G(S)alpha expression may also differ in the expression of certain cAMP-dependent genes.