View from the PEAKs: Insights from structural studies on the PEAK family of pseudokinases

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in structural biology Pub Date : 2024-09-24 DOI:10.1016/j.sbi.2024.102932

Isabelle S. Lucet , Roger J. Daly

引用次数: 0

Abstract

The PEAK family of pseudokinase scaffolds, comprising PEAK1 (originally termed SgK269), PEAK2 (SgK223, the human orthologue of rat Pragmin) and PEAK3 (C19orf35), have emerged as important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. These proteins undergo both homo- and heterotypic association that act to diversify signal output. Recently, structural and functional characterization of PEAK3 and its protein–protein interactions have shed light on PEAK signaling dynamics and the interdependency of PEAK family members, how PEAK dimerization regulates the binding of downstream effectors, and how 14-3-3 binding acts to regulate PEAK3 signal output. These important advances form the basis of this review.

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来自 PEAKs 的观点：PEAK 伪激酶家族结构研究的启示

伪激酶支架 PEAK 家族包括 PEAK1（原名 SgK269）、PEAK2（SgK223，大鼠 Pragmin 的人类直向同源物）和 PEAK3（C19orf35），它们已成为细胞信号传导的重要调节器和整合器，并在多种人类癌症中发挥致癌作用。这些蛋白会发生同型和异型结合，从而使信号输出多样化。最近，PEAK3 及其蛋白-蛋白相互作用的结构和功能特征研究揭示了 PEAK 信号动态和 PEAK 家族成员的相互依存关系、PEAK 二聚化如何调节下游效应物的结合以及 14-3-3 结合如何调节 PEAK3 信号输出。这些重要进展构成了本综述的基础。

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

Current opinion in structural biology 生物-生化与分子生物学

CiteScore

12.20

自引率

2.90%

发文量

179

审稿时长

6-12 weeks

期刊介绍： Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed. In COSB, we help the reader by providing in a systematic manner: 1. The views of experts on current advances in their field in a clear and readable form. 2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications. [...] The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance. -Folding and Binding- Nucleic acids and their protein complexes- Macromolecular Machines- Theory and Simulation- Sequences and Topology- New constructs and expression of proteins- Membranes- Engineering and Design- Carbohydrate-protein interactions and glycosylation- Biophysical and molecular biological methods- Multi-protein assemblies in signalling- Catalysis and Regulation