Macrophage-derived growth factors.

Macrophage-derived growth factors.
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DOI:
10.1007/978-3-642-77377-8_4
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发表时间:
1992
影响因子:
--
通讯作者:
D. Rappolee;D. Rappolee;Z. Werb
D. Rappolee;D. Rappolee;Z. Werb
中科院分区:
医学3区
文献类型:
--
作者:
D. Rappolee;D. Rappolee;Z. Werb

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在二十世纪初期的几十年里,生物学家试图在培养物中培养细胞。人们发现凝结的血液中含有实现这一目的的分子(Carrel 1912),但直到后来生物化学家才寻求纯化这些分子。到了本世纪中叶,生物化学家和生物学家试图用分子术语解释小鼠新生儿睁眼的现象(Cohen1987;Levi-Montalcini1987)。这些目标中的每一个最终都导致通过使用体外或体内生长生物测定和分离生化算法来分离称为生长因子的单一种类分子。表皮生长因子(EGF)、神经生长因子(NGF)、血小板源性生长因子(PDGF)、转化生长因子-β(TGF-β)、白细胞介素-1(IL-1)和巨噬细胞集落刺激因子(M-CSF或CSF-1)在20世纪70年代和20世纪80年代初通过这些方法被分离出来并直接测序或分子克隆(基于部分序列)。通过引入来自肿瘤的克隆转录物或基因片段来产生细胞转化灶,也产生了癌基因的亚类,这些癌基因被证明是生长因子[c-sis,或PDGF-B链,和卡波西肉瘤成纤维细胞生长因子(kFGF,或FGF-4)]。最近,细胞基因上游的高活性病毒启动子随机整合后体内肿瘤的形成产生了int-1和int-2(也称为FGF-3)生长因子。最后,在通过生物测定鉴定生长因子家族的创始成员后,可以使用低严格性 cDNA 文库筛选和聚合酶链式反应来完善该家族(JAKOWLEWet al. 1988;HEBERTet al. 1990)。所有生长因子都是可操作分离的,并根据其引起生长的能力来定义,但也可能充当非有丝分裂炎症因子。
In the early decades of the twentieth century biologists sought to grow cells in culture. Clotted blood was found to contain molecules that accomplished this purpose (Carrel 1912), but only later did biochemists seek to purify these molecules. By the middle of the century, biochemists and biologists sought to explain neonatal eye opening in mice in molecular terms (Cohen1987;Levi-Montalcini1987). Each of these goals ultimately led to the isolation of single species of molecules called growth factors by using in vitro or in vivo bioassays for growth and a biochemical algorithm for isolation. Epidermal growth factor (EGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), interleukin-1 (IL-1), and macrophage colony-stimulating factor (M-CSF, or CSF-1) were isolated and directly sequenced or molecularly cloned (based on partial sequences) by these means in the 1970s and early 1980s. The production of transformed foci of cells by introduction of fragments of cloned transcripts or genes from tumors also produced a subclass of oncogenes that turned out to be growth factors [c-sis, or PDGF-B chain, and Kaposi’s sarcoma-fibroblast growth factor (kFGF, or FGF-4)]. Most recently, the formation of tumors in vivo after random integration of a highly active viral promoter upstream of cellular genes has produced the int-1 and int-2 (also known as FGF-3) growth factors. Finally, after the founding member of a growth factor family is identified with a bioassay, low-stringency cDNA library screens and polymerase chain reaction can be used to complete the family (JAKOWLEWet al. 1988;HEBERTet al. 1990). All growth factors are operationally isolated and defined by their ability to cause growth, but may also act as nonmitogenic inflammatory factors.