The Role of PAK4 in Cytoskeletal and Cell Cycle Regulation
宋可 1陈丹丹 1李静宇 1杨晓葵 1马伟2
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作者信息
1. 首都医科大学附属北京妇产医院/北京妇幼保健院生殖医学科,北京 100026
2. 首都医科大学,北京 100069
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摘要
p21活化蛋白激酶(p21-activated protein kinase,PAK)是一类高度保守的丝氨酸/苏氨酸蛋白家族,是Rho家族小GTP酶的效应蛋白,参与多种信号通路传导.PAK4是PAK家族中最有代表性的成员,通过磷酸化下游底物,调控细胞骨架重组、细胞增殖和细胞周期进展等.PAK4过表达见于胰腺癌、胃癌和卵巢癌等多种肿瘤,参与肿瘤发生和肿瘤迁移等过程.研究PAK4的结构、作用机制对于揭示细胞周期调控和肿瘤生物学行为有重要价值.本文阐述和归纳了 PAK4的结构、激活过程及其在细胞骨架、细胞周期进展中的生物学作用,并综述了 PAK4调控妇科肿瘤发生发展以及PAK4抑制剂的最新研究进展.
Abstract
p21-activated protein kinase(PAK)is a highly conserved serine/threonine protein fam-ily that functions as an effector protein of the Rho family of small GTPases,playing crucial roles in multiple signaling pathways.Among the PAK family members,PAK4 stands out as the most representative,regulating cytoskeletal reorganization,cell proliferation,and cell cycle progres-sion through the phosphorylation of downstream substrates.PAK4 overexpression has been ob-served in a variety of tumors,including pancreatic cancer,gastric cancer,and ovarian cancer,im-plicating its involvement in pivotal processes such as tumorigenesis and metastasis.Investigating the structure and mechanism of PAK4 is of significant value in unraveling the regulation of the cell cycle and tumor biological behavior.This article elucidates and summarizes the structural characteristics,activation process,and biological roles of PAK4 in cytoskeletal dynamics and cell cycle progression.Additionally,it reviews the latest advancements in understanding PAK4 regu-lation in the initiation and development of gynecological tumors,as well as research progress in PAK4 inhibitors.
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