Laboratory of Cell and Developmental Signaling, NCI-Frederick, Frederick, Maryland 21702.
Cold Spring Harb Perspect Med. 2019 Jan 2;9(1):a033746. doi: 10.1101/cshperspect.a033746.
The extracellular signal-regulated kinase (ERK) cascade comprised of the Raf, MEK, and ERK protein kinases constitutes a key effector cascade used by the Ras GTPases to relay signals regulating cell growth, survival, proliferation, and differentiation. Of the ERK cascade components, the regulation of the Raf kinases is by far the most complex, involving changes in subcellular localization, protein and lipid interactions, as well as alterations in the Raf phosphorylation state. The Raf kinases interact directly with active, membrane-localized Ras, and this interaction is often the first step in the Raf activation process, which ultimately results in ERK activation and the downstream phosphorylation of cellular targets that will specify a particular biological response. Here, we will examine our current understanding of how Ras promotes Raf activation, focusing on the molecular mechanisms that contribute to the Raf activation/inactivation cycle.
细胞外信号调节激酶（ERK）级联反应由 Raf、MEK 和 ERK 蛋白激酶组成，是 Ras GTPases 用于传递信号调节细胞生长、存活、增殖和分化的关键效应级联反应。在 ERK 级联反应成分中，Raf 激酶的调节迄今为止是最复杂的，涉及细胞内定位、蛋白质和脂质相互作用的变化，以及 Raf 磷酸化状态的改变。Raf 激酶与活性的、膜定位的 Ras 直接相互作用，这种相互作用通常是 Raf 激活过程的第一步，最终导致 ERK 激活和细胞靶标的下游磷酸化，从而指定特定的生物学反应。在这里，我们将探讨我们目前对 Ras 如何促进 Raf 激活的理解，重点关注有助于 Raf 激活/失活循环的分子机制。
