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Ras p21作为非洲爪蟾卵母细胞中胰岛素作用的潜在介质。

Ras p21 as a potential mediator of insulin action in Xenopus oocytes.

作者信息

Korn L J, Siebel C W, McCormick F, Roth R A

出版信息

Science. 1987 May 15;236(4803):840-3. doi: 10.1126/science.3554510.

DOI:10.1126/science.3554510
PMID:3554510
Abstract

The oncogene protein product (p21) of the ras gene has been implicated in mediating the effects of a variety of growth factors and hormones. Microinjection of monoclonal antibody 6B7, which is directed against a synthetic peptide corresponding to a highly conserved region of p21 (amino acids 29 to 44) required for p21 function, specifically inhibited Xenopus oocyte maturation induced by incubation with insulin. The inhibition was dose-dependent and specific since (i) the same antibody had no effect on progesterone-induced maturation, (ii) immunoprecipitation and Western blotting indicated that the antibody recognized a single protein of molecular weight 21,000 in oocyte extracts, and (iii) inhibition was not observed with identical concentrations of normal immunoglobulin. Thus, p21 appears to be involved in mediating insulin-induced maturation of Xenopus oocytes. Furthermore, the mechanism may involve phosphorylation of p21, as p21 was found to be a substrate of the insulin receptor kinase.

摘要

ras基因的癌基因蛋白产物(p21)被认为在介导多种生长因子和激素的作用中发挥作用。微注射针对与p21功能所需的高度保守区域(氨基酸29至44)相对应的合成肽的单克隆抗体6B7,可特异性抑制胰岛素孵育诱导的非洲爪蟾卵母细胞成熟。这种抑制是剂量依赖性的且具有特异性,原因如下:(i)相同抗体对孕酮诱导的成熟没有影响;(ii)免疫沉淀和蛋白质印迹表明该抗体在卵母细胞提取物中识别出一种分子量为21,000的单一蛋白质;(iii)相同浓度的正常免疫球蛋白未观察到抑制作用。因此,p21似乎参与介导胰岛素诱导的非洲爪蟾卵母细胞成熟。此外,该机制可能涉及p21的磷酸化,因为发现p21是胰岛素受体激酶的底物。

相似文献

1
Ras p21 as a potential mediator of insulin action in Xenopus oocytes.Ras p21作为非洲爪蟾卵母细胞中胰岛素作用的潜在介质。
Science. 1987 May 15;236(4803):840-3. doi: 10.1126/science.3554510.
2
Insulin induction of Xenopus laevis oocyte maturation is inhibited by monoclonal antibody against p21 ras proteins.针对p21 ras蛋白的单克隆抗体可抑制胰岛素诱导的非洲爪蟾卵母细胞成熟。
Mol Cell Biol. 1987 Mar;7(3):1285-8. doi: 10.1128/mcb.7.3.1285-1288.1987.
3
A peptide from the GAP-binding domain of the ras-p21 protein and azatyrosine block ras-induced maturation of Xenopus oocytes.
Anticancer Res. 1991 Jul-Aug;11(4):1373-8.
4
Antibodies to the ras gene product inhibit adenylate cyclase and accelerate progesterone-induced cell division in Xenopus laevis oocytes.针对ras基因产物的抗体可抑制腺苷酸环化酶,并加速非洲爪蟾卵母细胞中孕酮诱导的细胞分裂。
Mol Cell Biol. 1986 Feb;6(2):719-22. doi: 10.1128/mcb.6.2.719-722.1986.
5
A peptide from the GAP-binding domain of the ras-p21 protein as well as azatyrosine block ras-induced maturation of Xenopus oocytes.
Biochem Biophys Res Commun. 1991 Dec 31;181(3):1378-84. doi: 10.1016/0006-291x(91)92091-w.
6
Requirement of phospholipase C-catalyzed hydrolysis of phosphatidylcholine for maturation of Xenopus laevis oocytes in response to insulin and ras p21.
J Biol Chem. 1991 Apr 15;266(11):6825-9.
7
Oncogenic ras protein induces meiotic maturation of amphibian oocytes in the presence of protein synthesis inhibitors.
FEBS Lett. 1988 Jul 18;234(2):426-30. doi: 10.1016/0014-5793(88)80130-3.
8
The antibiotic azatyrosine suppresses progesterone or [Val12]p21 Ha-ras/insulin-like growth factor I-induced germinal vesicle breakdown and tyrosine phosphorylation of Xenopus mitogen-activated protein kinase in oocytes.
Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7654-8. doi: 10.1073/pnas.89.16.7654.
9
Transforming ras proteins accelerate hormone-induced maturation and stimulate cyclic AMP phosphodiesterase in Xenopus oocytes.转化型Ras蛋白可加速激素诱导的成熟过程,并刺激非洲爪蟾卵母细胞中的环磷酸腺苷磷酸二酯酶。
Mol Cell Biol. 1990 Apr;10(4):1689-96. doi: 10.1128/mcb.10.4.1689-1696.1990.
10
A similar pool of cyclic AMP phosphodiesterase in Xenopus oocytes is stimulated by insulin, insulin-like growth factor 1, and [Val12,Thr59]Ha-ras protein.
J Biol Chem. 1989 Jan 15;264(2):856-61.

引用本文的文献

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40 Years of RAS-A Historic Overview.40 年 RAS 研究史——全面回顾
Genes (Basel). 2021 May 1;12(5):681. doi: 10.3390/genes12050681.
2
Conserved insulin signaling in the regulation of oocyte growth, development, and maturation.保守的胰岛素信号传导在卵母细胞生长、发育和成熟的调节中。
Mol Reprod Dev. 2017 Jun;84(6):444-459. doi: 10.1002/mrd.22806. Epub 2017 Apr 24.
3
Ras oncogenes: split personalities.Ras癌基因:具有双重特性。
Nat Rev Mol Cell Biol. 2008 Jul;9(7):517-31. doi: 10.1038/nrm2438.
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Insulin signaling inhibits the 5-HT2C receptor in choroid plexus via MAP kinase.胰岛素信号通过丝裂原活化蛋白激酶抑制脉络丛中的5-羟色胺2C受体。
BMC Neurosci. 2003 Jun 9;4:10. doi: 10.1186/1471-2202-4-10.
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Protein kinase B/Akt is essential for the insulin- but not progesterone-stimulated resumption of meiosis in Xenopus oocytes.蛋白激酶B/Akt对于非洲爪蟾卵母细胞中胰岛素刺激而非孕酮刺激的减数分裂恢复至关重要。
Biochem J. 2003 Jan 15;369(Pt 2):227-38. doi: 10.1042/BJ20021243.
6
Speedy: a novel cell cycle regulator of the G2/M transition.Speedy:一种新型的G2/M期转换细胞周期调节因子。
EMBO J. 1999 Apr 1;18(7):1869-77. doi: 10.1093/emboj/18.7.1869.
7
Multiple docking sites on substrate proteins form a modular system that mediates recognition by ERK MAP kinase.底物蛋白上的多个对接位点形成一个模块化系统,介导ERK丝裂原活化蛋白激酶的识别。
Genes Dev. 1999 Jan 15;13(2):163-75.
8
The kinase Eg2 is a component of the Xenopus oocyte progesterone-activated signaling pathway.激酶Eg2是非洲爪蟾卵母细胞孕酮激活信号通路的一个组成部分。
EMBO J. 1998 Oct 1;17(19):5627-37. doi: 10.1093/emboj/17.19.5627.
9
Insulin-induced differentiation and modulation of neuronal thread protein expression in primitive neuroectodermal tumor cells is linked to phosphorylation of insulin receptor substrate-1.胰岛素诱导原始神经外胚层肿瘤细胞分化并调节神经元丝状蛋白表达,这与胰岛素受体底物-1的磷酸化有关。
J Mol Neurosci. 1995;6(2):91-108. doi: 10.1007/BF02736769.
10
Functional homology of protein kinases required for sexual differentiation in Schizosaccharomyces pombe and Saccharomyces cerevisiae suggests a conserved signal transduction module in eukaryotic organisms.粟酒裂殖酵母和酿酒酵母性别分化所需蛋白激酶的功能同源性表明真核生物中存在一个保守的信号转导模块。
Mol Biol Cell. 1993 Jan;4(1):107-20. doi: 10.1091/mbc.4.1.107.