Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis, and tumorigenicity.
Insulin-like growth factor-I receptor. Its role in cell proliferation, apoptosis, and tumorigenicity.
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发表时间：
1995-09
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通讯作者：
R. Rubin;R. Baserga
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作者：
R. Rubin;R. Baserga
从细胞生长的观点来看，由其配体激活的IGF-IR具有三个重要功能：（a）它是体内和体外最佳生长所必需的，尽管即使在其不存在的情况下也会发生一些生长;（B）它对于转化表型的建立和维持以及对于几种类型的细胞的肿瘤发生是必需的;和（c）在体内和体外保护细胞免于凋亡。IGF-I受体似乎在这些过程中发挥了核心作用。而过表达的IGF-I受体仅对IGF-I具有促有丝分裂作用，并可完全转化和保护细胞免于凋亡，但对于过表达的EGF和PDGF受体则不能这么说（205，206）。这两种受体既不能诱导生长，也不能转化大多数缺乏IGF-I受体的细胞。当IGF-I受体水平被人为降低时发生的转化表型的逆转和细胞凋亡的诱导也指出了受体在这三个过程中的重要作用。这方面的一个重要区别是，在转化中重要的不是过表达的IGF-I受体，而是缺乏它不允许转化的表型。如果我们希望使用IGF-IR作为治疗干预的方法，这种区别是非常重要的。回到更基本的问题，IGF-I受体的突变分析表明，特定的结构域参与其促有丝分裂或促进转化的能力，这两个过程可以在受体本身的水平上分开。这一发现提出了一个关键问题：转化活性是否使用与促有丝分裂信号通路不同的通路？或者，这仅仅是一个数量效应的问题吗？这个问题的答案可能是对转化机制的一个非常重要的贡献。关于IGF-I受体保护细胞免于凋亡的机制知之甚少;这里再次提出了一些基本问题。在受体中是否存在具有抗凋亡活性的特定结构域？这种活动是否与有丝分裂和/或转化有关？信号转导通路中的哪些元件参与IGF-I受体的这三种不同功能？尽管许多问题仍未解决，但在过去几年中，IGF-I受体在正常和异常生长中的重要性迅速上升。（400字处截断摘要）
From the point of view of cell growth, the IGF-IR activated by its ligands has three important functions: (a) it is required for optimal growth both in vivo and in vitro, although some growth occurs even in its absence; (b) it is obligatory for the establishment and maintenance of the transformed phenotype and for tumorigenesis for several types of cells; and (c) it protects cells from apoptosis, both in vivo and in vitro. The IGF-I receptor does seem to occupy a central role in these processes. Whereas an overexpressed IGF-I receptor is mitogenic for IGF-I alone and is fully transforming and protects cells from apoptosis, the same cannot be said for overexpressed EGF and PDGF receptors (205, 206). These two receptors can neither induce growth or transform most cells lacking IGF-I receptors. The reversal of the transformed phenotype and the induction of apoptosis that occur when the levels of IGF-I receptors are artificially decreased also point out the essential role of the receptor in these three processes. An important distinction in this regard is that it is not so much an overexpressed IGF-I receptor that is important in transformation but the lack of it that does not allow the transformed phenotype. This distinction is extremely important if we wish to use the IGF-IR as an approach to therapeutic interventions. Returning to more basic questions, a mutational analysis of the IGF-I receptor has shown that specific domains are involved in its mitogenicity or its ability to facilitate transformation and that these two processes can be separated at the level of the receptor itself. This finding raises a crucial question: Is the transforming activity using a pathway that is separate from the mitogenic signaling pathway? Alternatively, is it simply a question of a quantitative effect? The answer to this question could be a very important contribution to the mechanism of transformation. Little is known about the mechanism(s) by which the IGF-I receptor protects cells from apoptosis; here again, some fundamental questions can be raised. Are there specific domains in the receptor for its antiapoptotic activity? Is this activity tied to mitogenesis and/or transformation? Which elements in the signal transduction pathway are involved in these three different functions of the IGF-I receptor? Although many problems are still unresolved, the last few years have seen a very rapid rise in the importance of the IGF-I receptor in both normal and abnormal growth.(ABSTRACT TRUNCATED AT 400 WORDS)