IGF binding proteins: regulation of cellular actions.

IGF binding proteins: regulation of cellular actions.
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DOI:
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发表时间:
1992-06
期刊:
Growth regulation
影响因子:
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通讯作者:
D. R. Clemmons
D. R. Clemmons
中科院分区:
其他
文献类型:
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作者:
D. R. Clemmons

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最近对六种形式的胰岛素样生长因子结合蛋白的纯化和结构分析开辟了在细胞水平研究其作用机制的可能性。虽然已经发表了大量关于细胞控制这些蛋白质分泌的信息,但它们对 IGF 靶细胞作用的调节仍未完全研究。 IGFBP-1 和 3 均已被证明是双电位调节剂。使用一组培养条件,两种蛋白质似乎都能抑制 IGF 介导的生长,而如果使用其他条件,它们似乎会刺激生长。尽管已经发表了几项表明 IGFBP-2 抑制生长的研究,但 IGFBP-2、5 和 6 在这方面的研究还较少。 IGFBP-4 似乎始终具有抑制作用,迄今为止尚未发表显示刺激作用的研究。最近的研究集中在这些双功能效应的原因上。显然,粘附细胞表面的能力似乎是这些蛋白质的一项重要特性,导致它们具有增强或抑制生长的能力。同样,IGFBP-1 在丝氨酸残基上的磷酸化似乎是一种结构修饰变化,导致生长调节发生改变。毫无疑问,未来将会发现其他导致生物活性调节的翻译后修饰。
The recent purification and structural analysis of the six forms of insulin-like growth factor binding proteins has opened up the possibility of studying their mechanism of action at the cellular level. While a great deal of information has been published regarding control of secretion of these proteins by cells, their modulation of the target cell actions of the IGFs remains incompletely studied. Both IGFBP-1 and 3 have been shown to be bipotential regulators. Using one set of culture conditions, both proteins appear to inhibit IGF-mediated growth while if other conditions are used they appear to stimulate growth. IGFBP-2, 5 and 6 have been less well studied in this regard, although several studies showing growth inhibition with IGFBP-2 have been published. IGFBP-4 appears to be consistently inhibitory and no studies showing stimulation have been published to date. Recent research has focused on the reason for these bifunctional effects. Clearly the ability to adhere to cell surfaces appears to be one important property of these proteins that results in their ability to potentiate or inhibit growth. Likewise, phosphorylation of IGFBP-1 on serine residues appears to be a structurally modifying change which results in altered growth regulation. The future will no doubt uncover other post-translational modifications that result in modulation of biologic activity.