Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada, N1G 2W1.
Biochem J. 2012 Oct 1;447(1):1-16. doi: 10.1042/BJ20120769.
Shc (Src homology and collagen homology) proteins are considered prototypical signalling adaptors in mammalian cells. Consisting of four unique members, ShcA, B, C and D, and multiple splice isoforms, the family is represented in nearly every cell type in the body, where it engages in an array of fundamental processes to transduce environmental stimuli. Two decades of investigation have begun to illuminate the mechanisms of the flagship ShcA protein, whereas much remains to be learned about the newest discovery, ShcD. It is clear, however, that the distinctive modular architecture of Shc proteins, their promiscuous phosphotyrosine-based interactions with a multitude of membrane receptors, involvement in central cascades including MAPK (mitogen-activated protein kinase) and Akt, and unconventional contributions to oxidative stress and apoptosis all require intricate regulation, and underlie diverse physiological function. From early cardiovascular development and neuronal differentiation to lifespan determination and tumorigenesis, Shc adaptors have proven to be more ubiquitous, versatile and dynamic than their structures alone suggest.
Shc（Src 同源和胶原同源）蛋白被认为是哺乳动物细胞中典型的信号转导衔接蛋白。Shc 家族由四个独特的成员 ShcA、B、C 和 D 以及多种剪接异构体组成，几乎存在于体内的每一种细胞类型中，在那里它参与了一系列基本过程来转导环境刺激。二十年的研究已经开始阐明标志性的 ShcA 蛋白的机制，而对于最新的发现 ShcD，还有很多需要了解。然而，很明显，Shc 蛋白独特的模块结构、它们与多种膜受体的基于磷酸酪氨酸的混杂相互作用、参与包括 MAPK（丝裂原激活蛋白激酶）和 Akt 在内的核心级联反应，以及对氧化应激和细胞凋亡的非常规贡献，都需要精细的调节，并为不同的生理功能奠定基础。从早期心血管发育和神经元分化到寿命决定和肿瘤发生，Shc 衔接蛋白已被证明比其结构本身更为普遍、多功能和动态。
