Prominin-1-Radixin Axis controls hepatic gluconeogenesis by regulating PKA activity
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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 down-regulated. 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).
SUBMITTER: Ms. Hyun Lee
PROVIDER: S-SCDT-EMBOR-2019-49416-T | biostudies-other |
REPOSITORIES: biostudies-other
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