Signaling from RAS to RAF: The Molecules and Their Mechanisms.

IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI:10.1146/annurev-biochem-052521-040754
Hyesung Jeon, Emre Tkacik, Michael J Eck
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引用次数: 0

Abstract

RAF family protein kinases are a key node in the RAS/RAF/MAP kinase pathway, the signaling cascade that controls cellular proliferation, differentiation, and survival in response to engagement of growth factor receptors on the cell surface. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation, RAF activation by RAS and the SHOC2 phosphatase complex, and RAF engagement with HSP90-CDC37 chaperone complexes. These studies have important implications for pharmacologic targeting of the pathway. They reveal RAF in distinct regulatory states and show that the functional RAF switch is an integrated complex of RAF with its substrate (MEK) and a 14-3-3 dimer. Here we review these advances, placing them in the context of decades of investigation of RAF regulation. We explore the insights they provide into aberrant activation of the pathway in cancer and RASopathies (developmental syndromes caused by germline mutations in components of the pathway).

从 RAS 到 RAF 的信号传递:分子及其机制。
RAF家族蛋白激酶是RAS/RAF/MAP激酶通路中的一个关键节点,RAS/RAF/MAP激酶通路是控制细胞增殖、分化和存活的信号级联,可对细胞表面的生长因子受体的参与做出反应。在过去几年中,结构和生化研究使人们对 RAF 的自动调节、RAS 和 SHOC2 磷酸酶复合物对 RAF 的激活以及 RAF 与 HSP90-CDC37 合子复合物的接合有了新的认识。这些研究对该通路的药物靶向具有重要意义。它们揭示了处于不同调控状态的 RAF,并表明 RAF 的功能开关是 RAF 与其底物(MEK)和 14-3-3 二聚体的综合复合物。在此,我们回顾了这些研究进展,并将其置于数十年来对 RAF 调控的研究背景中。我们将探讨它们为癌症和 RAS 病(由该通路成分的种系突变引起的发育综合征)中该通路的异常激活提供的启示。预计《生物化学年刊》第 93 卷的最终在线出版日期为 2024 年 6 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annual review of biochemistry
Annual review of biochemistry 生物-生化与分子生物学
CiteScore
33.90
自引率
0.00%
发文量
31
期刊介绍: The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.
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