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两种导致异常转化的src蛋白的氨基末端序列。

NH2-terminal sequences of two src proteins that cause aberrant transformation.

作者信息

Garber E A, Hanafusa H

出版信息

Proc Natl Acad Sci U S A. 1987 Jan;84(1):80-4. doi: 10.1073/pnas.84.1.80.

DOI:10.1073/pnas.84.1.80
PMID:3025866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC304145/
Abstract

Two isolates of recovered avian sarcoma viruses (rASVs), rASV157 and rASV1702, transform cells in culture, but have greatly reduced in vivo tumorigenicity. The src proteins of rASV157 and rASV1702 have alterations within their NH2 termini, are not myristoylated, and have an altered subcellular localization. We have molecularly cloned and determined the nucleotide sequences of the src genes of rASV157 and rASV1702. We found that their src proteins have unusual NH2 termini: the rASV157 src protein NH2 terminus consists of 30 amino acids of the env signal peptide attached to Ser-6 of the src sequence, while the rASV1702 src protein NH2 terminus consists of 45 amino acids of the env signal peptide attached to Ala-76 of the src sequence. Expression of recombinant Rous sarcoma virus constructs containing the molecularly cloned rASV src genes produced src proteins with the same properties as those of the parental viruses. Our results suggest that the NH2-terminal structures are responsible for many unusual properties of the mutant src proteins.

摘要

两株恢复性禽肉瘤病毒(rASV),即rASV157和rASV1702,可在培养物中转化细胞,但体内致瘤性大大降低。rASV157和rASV1702的src蛋白在其NH2末端存在改变,未进行肉豆蔻酰化,且亚细胞定位发生改变。我们对rASV157和rASV1702的src基因进行了分子克隆并测定了其核苷酸序列。我们发现它们的src蛋白具有不寻常的NH2末端:rASV157的src蛋白NH2末端由与src序列的Ser-6相连的env信号肽的30个氨基酸组成,而rASV1702的src蛋白NH2末端由与src序列的Ala-76相连的env信号肽的45个氨基酸组成。含有分子克隆的rASV src基因的重组劳斯肉瘤病毒构建体的表达产生了具有与亲本病毒相同特性的src蛋白。我们的结果表明,NH2末端结构导致了突变src蛋白的许多异常特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/99552b4483f8/pnas00266-0099-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/4ac834882adb/pnas00266-0099-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/0bdd911d3cf1/pnas00266-0099-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/99552b4483f8/pnas00266-0099-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/4ac834882adb/pnas00266-0099-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/0bdd911d3cf1/pnas00266-0099-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d10/304145/99552b4483f8/pnas00266-0099-c.jpg

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引用本文的文献

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The first seven amino acids encoded by the v-src oncogene act as a myristylation signal: lysine 7 is a critical determinant.

本文引用的文献

1
Molecular cloning and characterization of avian sarcoma virus UR2 and comparison of its transforming sequence with those of other avian sarcoma viruses.禽肉瘤病毒UR2的分子克隆与特性分析及其转化序列与其他禽肉瘤病毒转化序列的比较。
J Virol. 1984 Jun;50(3):914-21. doi: 10.1128/JVI.50.3.914-921.1984.
2
Size-variant pp60src proteins of recovered avian sarcoma viruses interact with adhesion plaques as peripheral membrane proteins: effects on cell transformation.恢复的禽肉瘤病毒的大小可变的pp60src蛋白作为外周膜蛋白与粘着斑相互作用:对细胞转化的影响。
Mol Cell Biol. 1984 Mar;4(3):454-67. doi: 10.1128/mcb.4.3.454-467.1984.
3
v-src癌基因编码的前七个氨基酸充当豆蔻酰化信号:赖氨酸7是关键决定因素。
Mol Cell Biol. 1988 Jun;8(6):2435-41. doi: 10.1128/mcb.8.6.2435-2441.1988.
4
Suppression of Rous sarcoma virus-induced tumor formation by preinfection with viruses encoding src protein with novel N termini.用编码具有新型N端的src蛋白的病毒进行预感染可抑制劳氏肉瘤病毒诱导的肿瘤形成。
J Virol. 1989 Jun;63(6):2461-8. doi: 10.1128/JVI.63.6.2461-2468.1989.
5
Phosphorylation of cellular proteins in Rous sarcoma virus-infected cells: analysis by use of anti-phosphotyrosine antibodies.劳氏肉瘤病毒感染细胞中细胞蛋白的磷酸化:使用抗磷酸酪氨酸抗体进行分析。
Mol Cell Biol. 1988 Aug;8(8):3035-42. doi: 10.1128/mcb.8.8.3035-3042.1988.
6
A mutation in v-src that removes a single conserved residue in the SH-2 domain of pp60v-src restricts transformation in a host-dependent manner.v-src 中的一个突变会去除 pp60v-src 的 SH-2 结构域中的一个保守残基,这种突变以宿主依赖的方式限制转化。
J Virol. 1989 Jan;63(1):338-48. doi: 10.1128/JVI.63.1.338-348.1989.
7
Role of gag sequence in the biochemical properties and transforming activity of the avian sarcoma virus UR2-encoded gag-ros fusion protein.gag序列在禽肉瘤病毒UR2编码的gag-ros融合蛋白的生化特性及转化活性中的作用
J Virol. 1990 Dec;64(12):5997-6009. doi: 10.1128/JVI.64.12.5997-6009.1990.
8
Two point mutations in the transmembrane domain of P68gag-ros inactive its transforming activity and cause a delay in membrane association.P68gag-ros跨膜结构域中的两个点突变使其转化活性失活,并导致膜结合延迟。
J Virol. 1991 Jan;65(1):180-9. doi: 10.1128/JVI.65.1.180-189.1991.
9
Analysis of cDNAs of the proto-oncogene c-src: heterogeneity in 5' exons and possible mechanism for the genesis of the 3' end of v-src.原癌基因c-src的cDNA分析:5'外显子的异质性及v-src 3'末端产生的可能机制。
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Identification of the viral sequence required for the generation of recovered avian sarcoma viruses and characterization of a series of replication-defective recovered avian sarcoma viruses.
鉴定产生恢复性禽肉瘤病毒所需的病毒序列,并对一系列复制缺陷型恢复性禽肉瘤病毒进行特性分析。
J Virol. 1984 Mar;49(3):881-91. doi: 10.1128/JVI.49.3.881-891.1984.
4
DNA sequence of the Bryan high-titer strain of Rous sarcoma virus: extent of env deletion and possible genealogical relationship with other viral strains.劳氏肉瘤病毒布莱恩高滴度毒株的DNA序列:env缺失程度以及与其他病毒毒株可能的谱系关系。
J Virol. 1984 Feb;49(2):549-56. doi: 10.1128/JVI.49.2.549-556.1984.
5
Local mutagenesis of Rous sarcoma virus: the major sites of tyrosine and serine phosphorylation of pp60src are dispensable for transformation.劳氏肉瘤病毒的局部诱变:pp60src 酪氨酸和丝氨酸磷酸化的主要位点对于转化并非必需。
Cell. 1983 Sep;34(2):597-607. doi: 10.1016/0092-8674(83)90392-6.
6
New M13 vectors for cloning.用于克隆的新型M13载体。
Methods Enzymol. 1983;101:20-78. doi: 10.1016/0076-6879(83)01005-8.
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Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product.劳氏肉瘤病毒env基因的完整序列:其产物结构和功能区域的鉴定
J Virol. 1983 Jun;46(3):920-36. doi: 10.1128/JVI.46.3.920-936.1983.
8
Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus.与劳氏肉瘤病毒src基因同源的细胞基因的结构与序列以及产生转化病毒的机制。
Cell. 1983 Mar;32(3):881-90. doi: 10.1016/0092-8674(83)90073-9.
9
Nucleotide sequence of Rous sarcoma virus.劳氏肉瘤病毒的核苷酸序列。
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10
Only membrane-associated RSV src proteins have amino-terminally bound lipid.只有与膜相关的呼吸道合胞病毒src蛋白在氨基末端结合了脂质。
Nature. 1983 Mar 10;302(5904):161-3. doi: 10.1038/302161a0.