Function of a complex of p-Y42 RhoA GTPase and pyruvate kinase M2 in EGF signaling pathway in glioma cells.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Neurochemistry Pub Date : 2024-08-25 DOI:10.1111/jnc.16210
Yoon-Beom Lee, Yohan Park, Amir Hamza, Jung Ki Min, Oyungerel Dogsom, Sung-Chan Kim, Jae-Bong Park
{"title":"Function of a complex of p-Y42 RhoA GTPase and pyruvate kinase M2 in EGF signaling pathway in glioma cells.","authors":"Yoon-Beom Lee, Yohan Park, Amir Hamza, Jung Ki Min, Oyungerel Dogsom, Sung-Chan Kim, Jae-Bong Park","doi":"10.1111/jnc.16210","DOIUrl":null,"url":null,"abstract":"<p><p>Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with β-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with β-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with β-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.</p>","PeriodicalId":16527,"journal":{"name":"Journal of Neurochemistry","volume":null,"pages":null},"PeriodicalIF":4.2000,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurochemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/jnc.16210","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Epidermal growth factor (EGF) is known to be a critical stimulant for inducing the proliferation of glioma cancer cells. In our study, we observed that GST-RhoA binds to pyruvate kinase M2 (PKM2) in vitro. While EGF reduced the levels of RhoA protein, it significantly increased p-Y42 RhoA, as well as PKM1 and PKM2 in LN18 glioma cell line. We determined that RhoA undergoes degradation through ubiquitination involving SCF1 and Smurf1. Interestingly, we observed that p-Y42 RhoA binds to PKM2, while the dephosphomimetic form, RhoA Y42F, did not. Additionally, our observation revealed that PKM2 stabilized both RhoA and p-Y42 RhoA. Importantly, RhoA, p-Y42 RhoA, and PKM2, but not RhoA-GTP, were localized in the nucleus upon EGF stimulation. Knockdown of RhoA with siRNA resulted in the reduced levels of phosphoglycerate kinase1 (PGK1) and microtubule affinity-regulating kinase 4 (MARK). Furthermore, we found that the promoter of PGK1 was associated with β-catenin and YAP. Notably, p-Y42 RhoA and PKM2 co-immunoprecipitated with β-catenin and YAP. Based on these findings, we proposed a novel mechanism by which p-Y42 RhoA and PKM2, in conjunction with β-catenin and YAP, regulate PGK1 expression, contributing to the progression of glioma upon EGF.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
胶质瘤细胞中 p-Y42 RhoA GTPase 和丙酮酸激酶 M2 复合物在 EGF 信号通路中的功能。
众所周知,表皮生长因子(EGF)是诱导胶质瘤癌细胞增殖的重要刺激物。在我们的研究中,我们观察到 GST-RhoA 在体外与丙酮酸激酶 M2(PKM2)结合。虽然 EGF 降低了 RhoA 蛋白的水平,但却显著增加了 LN18 脑胶质瘤细胞系中的 p-Y42 RhoA 以及 PKM1 和 PKM2。有趣的是,我们观察到 p-Y42 RhoA 能与 PKM2 结合,而去磷酸化形式的 RhoA Y42F 却不能。此外,我们的观察还发现,PKM2 能稳定 RhoA 和 p-Y42 RhoA。重要的是,在 EGF 刺激下,RhoA、p-Y42 RhoA 和 PKM2(而不是 RhoA-GTP)定位于细胞核中。用 siRNA 敲除 RhoA 会导致磷酸甘油酸激酶 1(PGK1)和微管亲和调节激酶 4(MARK)的水平降低。此外,我们还发现 PGK1 的启动子与 β-catenin 和 YAP 相关。值得注意的是,p-Y42 RhoA和PKM2与β-catenin和YAP共免疫沉淀。基于这些发现,我们提出了一种新的机制,即p-Y42 RhoA和PKM2与β-catenin和YAP共同调控PGK1的表达,从而在EGF作用下促进胶质瘤的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
期刊最新文献
Causal association between insulin sensitivity index and Alzheimer's disease. Circulating medium- and long-chain acylcarnitines are associated with plasma P-tau181 in cognitively normal older adults. Cross-species translational paradigms for assessing positive valence system as defined by the RDoC matrix. o1 and Gαo1/Gαo2 deletion differentially affect hippocampal mossy fiber tract anatomy and neuronal morphogenesis. Association of serum lipidomic profiles with risk of intracranial aneurysm: A Mendelian randomization study.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1