School of Biomedical Sciences, The University of Queensland, St Lucia, Qld, Australia; Oncogenic Signalling and Growth Control Program, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia; Department of Pathology, The University of Melbourne, Parkville, Vic., Australia.
FEBS J. 2013 Nov;280(21):5258-68. doi: 10.1111/febs.12509. Epub 2013 Sep 23.
To influence physiology and pathophysiology, G protein-coupled receptors (GPCRs) have evolved to appropriate additional signalling modalities, such as activation of adjacent membrane receptors. Epidermal growth factor receptors (EGFRs) mediate growth and remodelling actions of GPCRs, although the precise network of gene products and molecular cascades linking GPCRs to EGFRs (termed EGFR transactivation) remains incomplete. In this review, we describe the current view of GPCR-EGFR transactivation, identifying the established models of receptor cross-talk. We consider the limitations in our current knowledge, and propose that recent advances in molecular and cell biology technology, including functional genomics approaches, will allow a renewed focus of efforts to understand the mechanism underlying EGFR transactivation. Using an unbiased approach for identification of the molecules required for GPCR-mediated EGFR transactivation will provide a contemporary and more complete representation from which to extrapolate therapeutic control in diseases from cardiovascular remodelling to cancer.
为了影响生理学和病理生理学，G 蛋白偶联受体（GPCR）已经进化出适当的附加信号模式，例如激活相邻的膜受体。表皮生长因子受体（EGFR）介导 GPCR 的生长和重塑作用，尽管将 GPCR 与 EGFR 联系起来的基因产物和分子级联的确切网络（称为 EGFR 反式激活）尚不完全清楚。在这篇综述中，我们描述了 GPCR-EGFR 反式激活的当前观点，确定了受体串扰的既定模型。我们考虑了我们当前知识的局限性，并提出，包括功能基因组学方法在内的分子和细胞生物学技术的最新进展将使人们能够重新集中精力理解 EGFR 反式激活的机制。使用一种无偏的方法来鉴定 GPCR 介导的 EGFR 反式激活所需的分子，将提供一个更现代、更完整的代表性，从中可以推断出从心血管重塑到癌症等疾病的治疗控制。
