https://scholars.lib.ntu.edu.tw/handle/123456789/627048
標題: | Phosphorylation of Arl4A/D promotes their binding by the HYPK chaperone for their stable recruitment to the plasma membrane | 作者: | Lin, Ming-Chieh Yu, Chia-Jung FANG-JEN LEE |
關鍵字: | Arf-like GTPase; HYPK; Pak1; cell migration; protein stability | 公開日期: | 26-七月-2022 | 出版社: | National Academy of Sciences | 卷: | 119 | 期: | 30 | 來源出版物: | Proceedings of the National Academy of Sciences of the United States of America | 摘要: | The Arl4 small GTPases participate in a variety of cellular events, including cytoskeleton remodeling, vesicle trafficking, cell migration, and neuronal development. Whereas small GTPases are typically regulated by their GTPase cycle, Arl4 proteins have been found to act independent of this canonical regulatory mechanism. Here, we show that Arl4A and Arl4D (Arl4A/D) are unstable due to proteasomal degradation, but stimulation of cells by fibronectin (FN) inhibits this degradation to promote Arl4A/D stability. Proteomic analysis reveals that FN stimulation induces phosphorylation at S143 of Arl4A and at S144 of Arl4D. We identify Pak1 as the responsible kinase for these phosphorylations. Moreover, these phosphorylations promote the chaperone protein HYPK to bind Arl4A/D, which stabilizes their recruitment to the plasma membrane to promote cell migration. These findings not only advance a major mechanistic understanding of how Arl4 proteins act in cell migration but also achieve a fundamental understanding of how these small GTPases are modulated by revealing that protein stability, rather than the GTPase cycle, acts as a key regulatory mechanism. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/627048 | ISSN: | 00278424 | DOI: | 10.1073/pnas.2207414119 |
顯示於: | 分子醫學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。