THE ROLE OF FIBROBLAST GROWTH-FACTORS IN EARLY XENOPUS DEVELOPMENT

THE ROLE OF FIBROBLAST GROWTH-FACTORS IN EARLY XENOPUS DEVELOPMENT
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DOI:
10.1042/bst0220585
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发表时间:
1994-08-01
影响因子:
3.9
通讯作者:
ISAACS, HV
ISAACS, HV
中科院分区:
生物学3区
文献类型:
--
作者:
SLACK, JMW;ISAACS, HV

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ICRF Developmental Biology Unit,Department of Zoology,Oxford University,South Parks Road,Oxford OX I 3 PS,UK 1;成纤维细胞生长因子(FGF)形成一个多基因家族,目前已知包含9个成员。FGF是单链多肽,分子量在~ 15和40 kDa之间,其与肝素紧密结合并对适当的细胞类型具有多种重要的生物活性,包括有丝分裂发生、趋化性和神经元存活[11]。已知酪氨酸激酶类的四种受体以及一些其它结合蛋白。因子和受体之间存在高度的交叉反应性,但特定FGF和受体剪接形式之间也存在一些特异性[21]。FGF与受体的有效结合需要细胞表面硫酸乙酰肝素的参与,并导致受体分子的二聚化和酪氨酸激酶的活化。这导致信号转导途径的激活,导致丝裂原活化蛋白激酶,其包括原癌基因罗斯和ruf 13 I的产物。尽管对IXF的生物化学和ziitro活动有相当多的了解,但对其在完整动物中的作用仍然了解相对较少。在这方面,我们很幸运地拥有非洲爪蟾胚胎,因为这已经证明是一个非常有利的系统,在其中研究生长因子家族的体内作用。
ICRF Developmental Biology Unit, Department of Zoology, Oxford University, South Parks Road, Oxford OX I 3PS, UK1; ibroblast growth factors (FGFs) form a multigene family, at present known to contain nine members. 1 he FGFs are single-chain polypeptides, with molecular masses of between-15 and 40 kDa, that bind tightly to heparin and have a variety of important biological activities on appropriate cell types, including mitogenesis, chemotaxis and neuronal survival [11. Four receptors of the tyrosine kinase class are known together with some other binding proteins. There is a high degree of cross-reactivity between factors and receptors, but also some specificity between particular FGFs and receptor splice forms [21. Productive binding of FGF to the receptor requires the participation of cell-surface heparan sulphate, and causes the dimerization of receptor molecules and the activation of the tyrosine kinase. This leads to an activation of the signal transduction pathway leading to mitogen-activated protein kinase, which includes the products of the proto-oncogenes rus and ruf 13 I. Ikspite considerable knowkdge of the biochemistry and in ziitro activities of the IXFs, there is still a relatively poor understanding of their role in the intact animal. In this respect ue are fortunate in having at our disposal the Xenopus embryo, because this has turned out to offer a very favourable system in which to investigate the in vivo role of a family of growth factors.