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一种人骨肉瘤细胞系分泌一种生长因子,其结构与血小板衍生生长因子A链同二聚体相关。

A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains.

作者信息

Heldin C H, Johnsson A, Wennergren S, Wernstedt C, Betsholtz C, Westermark B

出版信息

Nature. 1986;319(6053):511-4. doi: 10.1038/319511a0.

DOI:10.1038/319511a0
PMID:3456080
Abstract

Platelet-derived growth factor (PDGF), as purified from fresh human platelets, is a protein of relative molecular mass (Mr) 30,000 composed of two disulphide-linked subunit chains of similar size, named A and B (ref. 1). The dimer structure of PDGRF seems to be important for its biological effects, as reduction irreversibly inactivates the factor; it is not known, however, whether PDGF exists as a heterodimer or as a mixture of homodimers. Amino-acid sequence analysis has revealed that the A- and B-chains of human PDGF are related to each other, and that the B-chain is almost identical to part of the v-sis gene product of simian sarcoma virus (SSV). There is experimental evidence that a PDGF-like protein is indeed operational in SSV-induced transformation and the biologically active v-sis product is probably structurally similar to a putative dimer of PDGF B-chains. PDGF-like growth factors and/or a 4.2-kilobase (kb) c-sis transcript are present in several transformed mammalian cell lines and in certain nontransformed cells; cloned c-sis complementary DNA from human T cells transformed with human T-lymphotropic virus (HTLV) or from human endothelial cells contains the coding sequence for a putative PDGF B-chain precursor, but apparently lacks PDGF A-chain sequences. We have previously partially purified and characterized a PDGF-like growth factor from U-2 OS cells (osteosarcoma-derived growth factor, ODGF) and shown that this factor has structural, functional and immunological characteristics in common with PDGF. We describe here a procedure for the preparation of homogeneous ODGF, and provide evidence that this factor, which binds to the PDGF receptor, has a structure similar to a homodimer of PDGF A-chains.

摘要

从新鲜人血小板中纯化得到的血小板源性生长因子(PDGF)是一种相对分子质量(Mr)为30,000的蛋白质,由两条大小相似的通过二硫键连接的亚基链组成,分别命名为A链和B链(参考文献1)。PDGRF的二聚体结构似乎对其生物学效应很重要,因为还原会不可逆地使该因子失活;然而,尚不清楚PDGF是以异二聚体形式存在还是以同二聚体混合物形式存在。氨基酸序列分析表明,人PDGF的A链和B链彼此相关,并且B链几乎与猿猴肉瘤病毒(SSV)的v-sis基因产物的一部分相同。有实验证据表明,一种类似PDGF的蛋白质确实在SSV诱导的转化中起作用,并且具有生物学活性的v-sis产物在结构上可能类似于PDGF B链的假定二聚体。几种转化的哺乳动物细胞系和某些未转化的细胞中存在类似PDGF的生长因子和/或4.2千碱基(kb)的c-sis转录本;从用人嗜T淋巴细胞病毒(HTLV)转化的人T细胞或人内皮细胞中克隆的c-sis互补DNA包含假定的PDGF B链前体的编码序列,但显然缺乏PDGF A链序列。我们之前已从U-2 OS细胞(骨肉瘤衍生生长因子,ODGF)中部分纯化并鉴定了一种类似PDGF的生长因子,并表明该因子具有与PDGF相同的结构、功能和免疫学特征。我们在此描述了一种制备均一ODGF的方法,并提供证据表明该与PDGF受体结合的因子具有与PDGF A链同二聚体相似的结构。

相似文献

1
A human osteosarcoma cell line secretes a growth factor structurally related to a homodimer of PDGF A-chains.一种人骨肉瘤细胞系分泌一种生长因子,其结构与血小板衍生生长因子A链同二聚体相关。
Nature. 1986;319(6053):511-4. doi: 10.1038/319511a0.
2
Chemical and biological properties of a growth factor from human-cultured osteosarcoma cells: resemblance with platelet-derived growth factor.人培养骨肉瘤细胞生长因子的化学和生物学特性:与血小板衍生生长因子的相似性
J Cell Physiol. 1980 Nov;105(2):235-46. doi: 10.1002/jcp.1041050207.
3
A high-molecular-weight PDGF-like factor secreted by v-sis transformed cells leads to growth stimulation and transformation.
Oncogene Res. 1988 May;2(4):311-24.
4
Alternative RNA splicing affects function of encoded platelet-derived growth factor A chain.可变RNA剪接影响编码的血小板衍生生长因子A链的功能。
Nature. 1987;328(6131):621-4. doi: 10.1038/328621a0.
5
cDNA clones reveal differences between human glial and endothelial cell platelet-derived growth factor A-chains.互补DNA克隆揭示了人类神经胶质细胞和内皮细胞血小板衍生生长因子A链之间的差异。
Nature. 1987;328(6131):619-21. doi: 10.1038/328619a0.
6
Platelet-derived growth factor: roles in normal and v-sis transformed cells.血小板衍生生长因子:在正常细胞和v-sis转化细胞中的作用。
Cancer Surv. 1985;4(4):633-53.
7
Detection of PDGF-2 homodimers in human tumor cells.人肿瘤细胞中血小板衍生生长因子-2同型二聚体的检测
Oncogene. 1987 Mar;1(1):79-85.
8
Integration of proviral DNA into the PDGF beta-receptor gene in HTLV-I-infected T-cells results in a novel tyrosine kinase product with transforming activity.在人嗜T淋巴细胞病毒I型(HTLV-I)感染的T细胞中,前病毒DNA整合到血小板衍生生长因子β受体(PDGF beta-受体)基因中,会产生一种具有转化活性的新型酪氨酸激酶产物。
Oncogene. 1997 Aug 28;15(9):1051-7. doi: 10.1038/sj.onc.1201267.
9
Platelet-derived growth factor in human malignancy.
Biofactors. 1992 Apr;3(4):217-27.
10
Identification and purification of PDGF/sis-like proteins from nuclei of simian sarcoma virus-transformed fibroblasts.
Oncogene Res. 1988 Feb;2(3):235-44.

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