White M F
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
Philos Trans R Soc Lond B Biol Sci. 1996 Feb 29;351(1336):181-9. doi: 10.1098/rstb.1996.0015.
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.
胰岛素受体底物（IRS）信号蛋白被胰岛素、胰岛素样生长因子-1（IGF-1）受体以及包括白细胞介素-4（IL-4）、白细胞介素-9（IL-9）和白细胞介素-13在内的各类细胞因子受体；干扰素α/β和干扰素γ；以及生长激素和白血病抑制因子（LIF）在酪氨酸残基上结合并磷酸化。IRS蛋白在这些受体与含有Src同源2结构域（SH2蛋白）的信号蛋白之间提供了一个界面。最近对IRS-2的鉴定为IRS蛋白的模块化结构和功能提供了新的见解。IRS蛋白通过消除大多数受体在将SH2蛋白直接招募到其自身磷酸化位点时遇到的化学计量限制，提供了一种信号放大的方式。此外，IRS蛋白使细胞内信号复合物与活化受体的内吞途径分离。多种受体对IRS蛋白的共同使用可能揭示各种激素和细胞因子之间以前未被认识、或虽被观察到但未得到解释的重要联系。基于IRS模式的其他信号分子很可能存在。
