Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
Mol Cell Biol. 2021 Mar 24;41(4). doi: 10.1128/MCB.00627-20.
SHOC2 is a prototypical leucine-rich repeat protein that promotes downstream receptor tyrosine kinase (RTK)/RAS signaling and plays important roles in several cellular and developmental processes. Gain-of-function germ line mutations of SHOC2 drive the RASopathy Noonan-like syndrome, and SHOC2 mediates adaptive resistance to mitogen-activated protein kinase (MAPK) inhibitors. Similar to many scaffolding proteins, SHOC2 facilitates signal transduction by enabling proximal protein interactions and regulating the subcellular localization of its binding partners. Here, we review the structural features of SHOC2 that mediate its known functions, discuss these elements in the context of various binding partners and signaling pathways, and highlight areas of SHOC2 biology where a consensus view has not yet emerged.
SHOC2 是一种典型的富含亮氨酸重复蛋白，可促进下游受体酪氨酸激酶 (RTK)/RAS 信号转导，并在多种细胞和发育过程中发挥重要作用。SHOC2 的功能获得性种系突变驱动 RASopathy 类诺南综合征，SHOC2 介导对丝裂原活化蛋白激酶 (MAPK) 抑制剂的适应性耐药。与许多支架蛋白类似，SHOC2 通过促进近端蛋白相互作用并调节其结合伙伴的亚细胞定位来促进信号转导。在这里，我们回顾了介导 SHOC2 已知功能的结构特征，讨论了这些元素在各种结合伙伴和信号通路中的作用，并强调了 SHOC2 生物学中尚未达成共识的领域。
