Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity
- Authors
- Lee, Hyun; Yu, Dong-Min; Park, Jun Sub; Lee, Hwayeon; Kim, Jun-Seok; Kim, Hong Lim; Koo, Seung-Hoi; Lee, Jae-Seon; Lee, Sungsoo; Ko, Young-Gyu
- Issue Date
- 5-11월-2020
- Publisher
- WILEY
- Keywords
- cAMP signaling; gluconeogenesis; Prominin& #8208; 1; protein kinase A; radixin
- Citation
- EMBO REPORTS, v.21, no.11
- Indexed
- SCIE
SCOPUS
- Journal Title
- EMBO REPORTS
- Volume
- 21
- Number
- 11
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/51830
- DOI
- 10.15252/embr.201949416
- ISSN
- 1469-221X
- Abstract
- Prominin-1 (Prom1) is a major cell surface marker of cancer stem cells, but its physiological functions in the liver have not been elucidated. We analyzed the levels of mRNA transcripts in serum-starved primary WT (Prom1(+/+)) and KO (Prom1(-/-)) mouse hepatocytes using RNA sequencing (RNA-seq) data, and found that CREB target genes were downregulated. This initial observation led us to determine that Prom1 deficiency inhibited cAMP response element-binding protein (CREB) activation and gluconeogenesis, but not cyclic AMP (cAMP) accumulation, in glucagon-, epinephrine-, or forskolin-treated liver tissues and primary hepatocytes, and mitigated glucagon-induced hyperglycemia. Because Prom1 interacted with radixin, Prom1 deficiency prevented radixin from localizing to the plasma membrane. Moreover, systemic adenoviral knockdown of radixin inhibited CREB activation and gluconeogenesis in glucagon-treated liver tissues and primary hepatocytes, and mitigated glucagon-elicited hyperglycemia. Based on these results, we conclude that Prom1 regulates hepatic PKA signaling via radixin functioning as an A kinase-anchored protein (AKAP).
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Collections - Graduate School > Department of Life Sciences > 1. Journal Articles
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