与受体相关的支架一般被认为是信号作用通道的相对静止的成分，它们将一个被激发的受体连接到下游目标上，同时增大该受体的范围和效能。其中的一个例子是支架蛋白Shc1，它与被激发的EGF受体酪氨酸激酶结合。在这项研究中，Tony Pawson及同事利用一种定量蛋白质组学方法发现，Shc1不只是一个简单的转接蛋白，它还连续吸收具有截然不同功能的蛋白，从而随着时间的推移切换EGF受体的信号输出。（生物谷Bioon.com）
生物谷推荐英文摘要：
Nature doi: 10.1038/nature12308
Temporal regulation of EGF signalling networks by the scaffold protein Shc1
Yong Zheng, Cunjie Zhang, David R. Croucher, Mohamed A. Soliman, Nicole St-Denis, Adrian Pasculescu, Lorne Taylor, Stephen A. Tate, W. Rod Hardy, Karen Colwill, Anna Yue Dai, Rick Bagshaw, James W. Dennis, Anne-Claude Gingras, Roger J. Daly & Tony Pawson
Cell-surface receptors frequently use scaffold proteins to recruit cytoplasmic targets, but the rationale for this is uncertain. Activated receptor tyrosine kinases, for example, engage scaffolds such as Shc1 that contain phosphotyrosine (pTyr)-binding (PTB) domains. Using quantitative mass spectrometry, here we show that mammalian Shc1 responds to epidermal growth factor (EGF) stimulation through multiple waves of distinct phosphorylation events and protein interactions. After stimulation, Shc1 rapidly binds a group of proteins that activate pro-mitogenic or survival pathways dependent on recruitment of the Grb2 adaptor to Shc1 pTyr sites. Akt-mediated feedback phosphorylation of Shc1 Ser?29 then recruits the Ptpn12 tyrosine phosphatase. This is followed by a sub-network of proteins involved in cytoskeletal reorganization, trafficking and signal termination that binds Shc1 with delayed kinetics, largely through the SgK269 pseudokinase/adaptor protein. Ptpn12 acts as a switch to convert Shc1 from pTyr/Grb2-based signalling to SgK269-mediated pathways that regulate cell invasion and morphogenesis. The Shc1 scaffold therefore directs the temporal flow of signalling information after EGF stimulation.
