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针对ras癌基因产物第12位氨基酸的特异性抗体可抑制GTP结合。

Antibodies specific for amino acid 12 of the ras oncogene product inhibit GTP binding.

作者信息

Clark R, Wong G, Arnheim N, Nitecki D, McCormick F

出版信息

Proc Natl Acad Sci U S A. 1985 Aug;82(16):5280-4. doi: 10.1073/pnas.82.16.5280.

DOI:10.1073/pnas.82.16.5280
PMID:3927300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC390551/
Abstract

An antibody (anti-p21ser) was raised against a ras p21-related synthetic peptide and was able to recognize specifically the substitution of serine for glycine at amino acid 12 of p21. This substitution causes oncogenic activation of p21. Anti-p21ser was found to immunoprecipitate v-Ki-ras p21 and to strongly inhibit its ability to autophosphorylate and to bind GTP in an immunoabsorption assay. Furthermore, binding of the antibody to p21 was specifically inhibited by GTP or GDP, suggesting that amino acids around position 12 are part of the GTP/GDP binding site. These results, taken together with the observation that the microinjection of anti-p21ser into cells transformed by v-Ki-ras p21 causes a transient reversion of the cells to a normal phenotype [Feramisco, J. R., Clark, R., Wong, G., Arnheim, N., Milley, R. & McCormick, F. (1985) Nature (London) 314, 639-642], support the idea that interaction of p21 with guanine nucleotides is crucial to the transforming function of this protein.

摘要

针对一种与ras p21相关的合成肽制备了一种抗体(抗p21ser),该抗体能够特异性识别p21第12位氨基酸处丝氨酸取代甘氨酸的情况。这种取代会导致p21的致癌激活。在免疫吸附试验中,发现抗p21ser能免疫沉淀v-Ki-ras p21,并强烈抑制其自身磷酸化和结合GTP的能力。此外,GTP或GDP能特异性抑制该抗体与p21的结合,这表明12位附近的氨基酸是GTP/GDP结合位点的一部分。这些结果,再加上将抗p21ser显微注射到由v-Ki-ras p21转化的细胞中会导致细胞短暂恢复到正常表型的观察结果[费拉米斯科,J.R.,克拉克,R.,王,G.,阿恩海姆,N.,米利,R.和麦科密克,F.(1985年)《自然》(伦敦)314,639 - 642],支持了p21与鸟嘌呤核苷酸的相互作用对该蛋白的转化功能至关重要这一观点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/5bac0aa8380b/pnas00356-0054-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/a4ed035dd9a6/pnas00356-0052-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/4b4d519c5b56/pnas00356-0052-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/119303118546/pnas00356-0052-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/a1df23964f91/pnas00356-0052-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/90825dc480bd/pnas00356-0052-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/2e913e930d49/pnas00356-0053-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/cc17d33b701f/pnas00356-0053-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/5bac0aa8380b/pnas00356-0054-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/a4ed035dd9a6/pnas00356-0052-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/4b4d519c5b56/pnas00356-0052-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/119303118546/pnas00356-0052-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/a1df23964f91/pnas00356-0052-d.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/90825dc480bd/pnas00356-0052-e.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/2e913e930d49/pnas00356-0053-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/cc17d33b701f/pnas00356-0053-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/094a/390551/5bac0aa8380b/pnas00356-0054-a.jpg

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本文引用的文献

1
Electrophoretic transfer of proteins and nucleic acids from slab gels to diazobenzyloxymethyl cellulose or nitrocellulose sheets.蛋白质和核酸从平板凝胶电泳转移至重氮苄氧基甲基纤维素或硝酸纤维素膜上。
Anal Biochem. 1980 Mar 1;102(2):459-71. doi: 10.1016/0003-2697(80)90182-7.
2
Structural features of the GDP binding site of elongation factor Tu from Escherichia coli as determined by x-ray diffraction.通过X射线衍射测定的大肠杆菌延伸因子Tu的GDP结合位点的结构特征。
FEBS Lett. 1981 Jun 29;129(1):177-9. doi: 10.1016/0014-5793(81)80784-3.
3
Acquisition of transforming properties by alternative point mutations within c-bas/has human proto-oncogene.
Biochem J. 2020 Aug 14;477(15):2893-2919. doi: 10.1042/BCJ20190839.
4
Biology, pathology, and therapeutic targeting of RAS.RAS 的生物学、病理学和治疗靶点。
Adv Cancer Res. 2020;148:69-146. doi: 10.1016/bs.acr.2020.05.002. Epub 2020 Jul 9.
5
Therapeutic targeting of RAS: New hope for drugging the "undruggable".靶向治疗 RAS:为“不可成药”带来新希望。
Biochim Biophys Acta Mol Cell Res. 2020 Feb;1867(2):118570. doi: 10.1016/j.bbamcr.2019.118570. Epub 2019 Oct 31.
6
Ras and Rap1: A tale of two GTPases.Ras 和 Rap1:两种 GTP 酶的故事。
Semin Cancer Biol. 2019 Feb;54:29-39. doi: 10.1016/j.semcancer.2018.03.005. Epub 2018 Apr 3.
7
Direct inhibition of RAS: Quest for the Holy Grail?直接抑制 RAS:圣杯的追寻?
Semin Cancer Biol. 2019 Feb;54:138-148. doi: 10.1016/j.semcancer.2017.12.005. Epub 2017 Dec 14.
8
Therapeutic strategies for targeting ras proteins.靶向Ras蛋白的治疗策略。
Genes Cancer. 2011 Mar;2(3):359-72. doi: 10.1177/1947601911412376.
9
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.
10
Heterologous expression and characterization of the human R-ras gene product.人类R-ras基因产物的异源表达与特性分析
Mol Cell Biol. 1987 Aug;7(8):2845-56. doi: 10.1128/mcb.7.8.2845-2856.1987.
c-bas/has人类原癌基因内的替代点突变导致转化特性的获得。
Nature. 1983 Jun 30;303(5920):775-9. doi: 10.1038/303775a0.
4
Predicted nucleotide-binding properties of p21 protein and its cancer-associated variant.p21蛋白及其癌症相关变体的预测核苷酸结合特性。
Nature. 1983 Apr 28;302(5911):842-4. doi: 10.1038/302842a0.
5
Mimicking the alloantigenicity of proteins with chemically synthesized peptides differing in single amino acids.用单氨基酸不同的化学合成肽模拟蛋白质的同种异体抗原性。
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6
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7
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8
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9
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