https://scholars.lib.ntu.edu.tw/handle/123456789/626674
標題: | AMPK promotes Arf6 activation in a kinase-independent manner upon glucose starvation | 作者: | Chen, Kuan-Jung JIA-WEI HSU FANG-JEN LEE |
關鍵字: | ADP-ribosylation factor; Cell invasion; GTPase; Glucose deprivation | 公開日期: | 15-九月-2022 | 出版社: | The Company of Biologists | 卷: | 135 | 期: | 18 | 起(迄)頁: | jcs259609 | 來源出版物: | Journal of cell science | 摘要: | AMP-activated protein kinase (AMPK) is a crucial cellular nutrient and energy sensor that maintains energy homeostasis. AMPK also governs cancer cell invasion and migration by regulating gene expression and activating multiple cellular signaling pathways. ADP-ribosylation factor 6 (Arf6) can be activated via nucleotide exchange by guanine-nucleotide-exchange factors (GEFs), and its activation also regulates tumor invasion and migration. By studying GEF-mediated Arf6 activation, we have elucidated that AMPK functions as a noncanonical GEF for Arf6 in a kinase-independent manner. Moreover, by examining the physiological role of the AMPK-Arf6 axis, we have determined that AMPK activates Arf6 upon glucose starvation and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) treatment. We have further identified the binding motif in the C-terminal regulatory domain of AMPK that is responsible for promoting Arf6 activation and, thus, inducing cell migration and invasion. These findings reveal a noncanonical role of AMPK in which its C-terminal regulatory domain serves as a GEF for Arf6 during glucose deprivation. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/626674 | ISSN: | 00219533 | DOI: | 10.1242/jcs.259609 |
顯示於: | 生化科學研究所 |
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。