c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology
2024-08-26
状态已发表
摘要c-Abl is a non-receptor tyrosine kinase involved in the regulation of cell migration and morphogenesis, but underlying mechanism remains unclear. Here, we report the identification of tight junction protein ZO-2 as a bona fide substrate of c-Abl. We show that c-Abl directly binds to and phosphorylates the C-terminus of ZO-2. In addition, c-Abl stimulates the activity of JAK1, which subsequently phosphorylates the N-terminus of ZO-2. Using the RNAi-mediated knockdown/rescue strategy, we demonstrate that c-Abl regulates cellular morphology and migration through targeting ZO-2 for phosphorylation. c-Abl activity is also associated with decreased traction forces exerted on the cell substrate and reduced monolayer tension, thus corroborating c-Abl kinase activity-mediated inhibition of cell migration. Collectively, our data uncover ZO-2 as a novel mediator for c-Abl-dependent regulation of cell migration.
语种英语
DOI10.1101/2024.08.25.609487
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出处bioRxiv
收录类别PPRN.PPRN
WOS记录号PPRN:91525112
WOS类目Cell Biology
文献类型预印本
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/415915
专题生命科学与技术学院
生命科学与技术学院_PI研究组_刘雪松组
通讯作者Choi, Doo Eun; Gweon, Bomi
作者单位
1.Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115, USA
2.Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114, USA
3.Harvard Med Sch, Dept Neurol, Boston, MA 02115, USA
4.Sejong Univ, Dept Mech Engn, Seoul 05006, South Korea
5.Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115, USA
6.Univ Wisconsin Madison, Dept Mech Engn, Madison, WI 53706, USA
7.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201203, Peoples R China
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GB/T 7714
Choi, Doo Eun,Gweon, Bomi,Notbohm, Jacob,et al. c-Abl Kinase Targets Tight Junction Protein ZO-2 in Regulation of Cell Migration and Morphology. 2024.
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