The IRS-signalling system in insulin and cytokine action.
The IRS-signalling system in insulin and cytokine action.
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DOI：
10.1098/rstb.1996.0015
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发表时间：
1996-02
期刊：
影响因子：
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通讯作者：
M. White
中科院分区：
文献类型：
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作者：
M. White
IRS信号蛋白被胰岛素和IGF-1受体，以及各种细胞因子受体，包括IL-4、IL-9和IL-13；干扰素α/β和干扰素伽马；生长激素和LIF参与并磷酸化在酪氨酸残基上。IRS-蛋白提供了这些受体和含有Src同源-2结构域的信号蛋白(SH2-蛋白)之间的接口。最近对IRS-2的鉴定为了解IRS-蛋白的模块结构和功能提供了新的视角。IRS-蛋白通过消除大多数受体所遇到的化学计量限制而提供了一种信号放大的手段，这些受体直接将SH2-蛋白招募到它们的自动磷酸化位点。此外，IRS蛋白将细胞内信号复合体从激活的受体的内吞途径中分离出来。多个受体共同使用IRS蛋白可能会揭示各种激素和细胞因子之间的重要联系，这些激素和细胞因子以前没有被识别，或者被观察到但无法解释。基于IRS范式的额外信号分子的存在是可能的。
IRS-signalling proteins are engaged and phosphorylated on tyrosine residues by the receptors for insulin and IGF-1, and various classes of cytokine receptors, including IL-4, IL-9, and IL-13; IFN alpha/beta and IFN gamma; and growth hormone and LIF. IRS-proteins provide an interface between these receptors and signalling proteins which contain Src homology-2 domains (SH2-proteins). The recent identification of IRS-2 provides new insight into the modular structure and function of the IRS-proteins. The IRS-proteins provide a means for signal amplification by eliminating the stoichiometric constraints encountered by most receptors which directly recruit SH2-proteins to their autophosphorylation sites. Moreover, IRS-proteins dissociate the intracellular signalling complex from the endocytic pathways of the activated receptor. The shared use of IRS-proteins by multiple receptors is likely to reveal important connections between various hormones and cytokines that were previously unrecognized,or observed but unexplained. The existence of additional signalling molecules based on the IRS-paradigm is likely.