Cattaneo E, Pelicci P G
Institute of Pharmacological Sciences, University of Milano, Italy.
Trends Neurosci. 1998 Nov;21(11):476-81. doi: 10.1016/s0166-2236(98)01282-x.
In mammalian systems, SH2-containing cytoplasmic signalling molecules are known to play an important role in determining cell responsiveness to the environment. In particular, following activation of a receptor protein tyrosine kinase (RPTK), proteins like Shc and Grb2 bind to phosphotyrosine residues of stimulated receptors, thereby activating downstream components of specific signalling pathways. The ShcA gene was identified in 1992 and was found to encode three proteins with properties of adaptor molecules coupling RPTKs to Ras. Early data obtained in non-neuronal cells have revealed that Shc and Grb2 proteins are highly expressed and activated in all cells. However, recent analyses of ShcA mRNA and protein in the developing brain revealed progressive downregulation of their expression during differentiation from neuroblasts to neurons. Conversely, the two newly identified Shc homologues (ShcB/Sli and ShcC/Rai) are highly expressed in the mature brain.Thus, variations in the intracellular levels of adaptor proteins might represent one of the mechanisms by which a differentiating cell changes its ability to respond to a given factor, allowing a cell to choose between proliferation and differentiation.
在哺乳动物系统中，已知含SH2结构域的细胞质信号分子在决定细胞对环境的反应性方面发挥重要作用。特别是，在受体蛋白酪氨酸激酶（RPTK）激活后，诸如Shc和Grb2等蛋白会与受刺激受体的磷酸酪氨酸残基结合，从而激活特定信号通路的下游成分。ShcA基因于1992年被鉴定出来，发现它编码三种具有衔接分子特性的蛋白，可将RPTK与Ras偶联。在非神经元细胞中获得的早期数据表明，Shc和Grb2蛋白在所有细胞中均高度表达并被激活。然而，最近对发育中的大脑中ShcA mRNA和蛋白的分析显示，从神经母细胞向神经元分化过程中，它们的表达逐渐下调。相反，两个新鉴定的Shc同源物（ShcB/Sli和ShcC/Rai）在成熟大脑中高度表达。因此，衔接蛋白细胞内水平的变化可能是分化细胞改变其对给定因子反应能力的机制之一，使细胞能够在增殖和分化之间做出选择。
