Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP.

Regulation of deactivation of photoreceptor G protein by its target enzyme and cGMP.
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通过其靶酶和CGMP对光感受器G蛋白的失活调节。

DOI:
10.1038/357416a0
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发表时间:
1992-06-04
期刊:
影响因子:
64.8
通讯作者:
Bownds MD
Bownds MD
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Arshavsky VYu;Bownds MD

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光感受器G蛋白,即转导蛋白,是一类异三聚体G蛋白中的一种,在膜受体和细胞内酶或离子通道之间起中介作用。光激活的视紫红质在多个转导蛋白分子上催化GDP交换GTP。激活的转导蛋白通过释放磷酸二酯酶γ-亚基的抑制作用刺激环GMP磷酸二酯酶。这导致杆状细胞中cGMP水平的降低,以及由cGMP - 1控制的质膜阳离子通道的关闭。在这种和其他系统中,关闭反应需要GTP结合到G蛋白上,通过内在的GTP酶活性水解5 - 7。在这里,我们报道了转导蛋白与cGMP磷酸二酯酶的相互作用,特别是与其γ-亚基的相互作用,使GTPase活性提高了几倍。因此,磷酸二酯酶的γ-亚基的功能类似于调节小gtp结合蛋白类的gtpase激活蛋白。cGMP可能通过磷酸二酯酶α和β-亚基的非催化cGMP结合位点部分抑制这种加速。这种cGMP调节可能在光响应的光适应中发挥作用,作为一种负反馈,由于光导致细胞质cGMP减少,减少了活化的cGMP磷酸二酯酶的寿命。
THE photoreceptor G protein, transducin, is one of the class of heterotrimeric G proteins that mediates between membrane receptors and intracellular enzymes or ion channels. Light-activated rhodopsin catalyses the exchange of GDP for GTP on multiple transducin molecules. Activated transducin then stimulates cyclic GMP phosphodiesterase by releasing an inhibitory action of the phosphodiesterase γ-subunits. This leads to a decrease in cGMP levels in the rod, and closure of plasma membrane cationic channels gated by cGMP1–4. In this and other systems, turn-off of the response requires the GTP bound to G protein to be hydrolysed by an intrinsic GTPase activity5–7. Here we report that the interaction of transducin with cGMP phosphodiesterase, specifically with its γ-subunits, accelerates GTPase activity by several fold. Thus the γ-subunits of the phosphodiesterase serve a function analogous to the GTPase-activating proteins that regulate the class of small GTP-binding proteins. The acceleration can be partially suppressed by cGMP, most probably through the non-catalytic cGMP-binding sites of phosphodiesterase α and β-subunits. This cGMP regulation may function in light-adaptation of the photo-response as a negative feedback that decreases the lifetime of activated cGMP phosphodiesterase as light causes decreases in cytoplasmic cGMP.
DOI: 10.1038/283587a0
发表时间: 1980-01-01
期刊: NATURE
影响因子: 64.8
作者:
KUHN, H
通讯作者: KUHN, H
DOI: 10.1073/pnas.87.1.288
发表时间: 1990-01-01
影响因子: 11.1
作者:
CHARBONNEAU, H;PRUSTI, RK;BEAVO, JA
通讯作者: BEAVO, JA
DOI: 10.1016/0014-5793(89)80754-9
发表时间: 1989-07-03
期刊: FEBS LETTERS
影响因子: 3.5
作者:
ARSHAVSKY, VY;ANTOCH, MP;PHILIPPOV, PP
通讯作者: PHILIPPOV, PP
DOI: 10.1126/science.1902986
发表时间: 1991-05-10
期刊: SCIENCE
影响因子: 56.9
作者:
SIMON, MI;STRATHMANN, MP;GAUTAM, N
通讯作者: GAUTAM, N
DOI: 10.1073/pnas.86.13.4922
发表时间: 1989-07-01
影响因子: 11.1
作者:
BROWN, RL;STRYER, L
通讯作者: STRYER, L