Department of Biochemistry and Molecular Biology, The University of Texas MD Anderson Cancer Center, Unit 1954, 1515 Holcombe Blvd, Houston, TX 77030, USA; Graduate School of Biological Sciences, The University of Texas MD Anderson Cancer Center, Unit 1954, 1515 Holcombe Blvd, Houston, TX 77030, USA.
School of Molecular and Cellular Biology, University of Leeds, LC Miall Building, Leeds, LS2 9JT, UK.
Int J Biochem Cell Biol. 2018 Jan;94:89-97. doi: 10.1016/j.biocel.2017.11.014. Epub 2017 Dec 5.
Scaffold proteins play important roles in regulating signalling network fidelity, the absence of which is often the basis for diseases such as cancer. In the present work, we show that the prototypical scaffold protein Shc is phosphorylated by the extracellular signal-regulated kinase, Erk. In addition, Shc threonine phosphorylation is specifically up-regulated in two selected triple-negative breast cancer (TNBC) cell lines. To explore how Erk-mediated threonine phosphorylation on Shc might play a role in the dysregulation of signalling events, we investigated how Shc affects pathways downstream of EGF receptor. Using an in vitro model and biophysical analysis, we show that Shc threonine phosphorylation is responsible for elevated Akt and Erk signalling, potentially through the recruitment of the 14-3-3 ζ and Pin-1 proteins.
支架蛋白在调节信号网络保真度方面发挥着重要作用，其缺失通常是癌症等疾病的基础。在本工作中，我们表明，典型的支架蛋白 Shc 被细胞外信号调节激酶 Erk 磷酸化。此外，Shc 苏氨酸磷酸化在两种选定的三阴性乳腺癌（TNBC）细胞系中特异性上调。为了探索 Erk 介导的 Shc 上的苏氨酸磷酸化如何在信号事件的失调中发挥作用，我们研究了 Shc 如何影响 EGF 受体下游的途径。使用体外模型和生物物理分析，我们表明 Shc 苏氨酸磷酸化负责升高 Akt 和 Erk 信号，可能是通过招募 14-3-3 ζ 和 Pin-1 蛋白。
