Cdc2-like Kinase 2 Is an Insulin-Regulated Suppressor of Hepatic Gluconeogenesis

Joseph T. Rodgers, Wilhelm Haas, Steven P. Gygi, Pere Puigserver

Research output: Contribution to journalArticle

Abstract

Dynamic regulation of insulin signaling and metabolic gene expression is critical to nutrient homeostasis; dysregulation of these pathways is widely implicated in insulin resistance and other disease states. Though the metabolic effects of insulin are well established, the components linking insulin signal transduction to a metabolic response are not as well understood. Here, we show that Cdc2-like kinase 2 (Clk2) is an insulin-regulated suppressor of hepatic gluconeogenesis and glucose output. Clk2 protein levels and kinase activity are induced as part of the hepatic refeeding response by the insulin/Akt pathway. Clk2 directly phosphorylates the SR domain on PGC-1α, resulting in repression of gluconeogenic gene expression and hepatic glucose output. In addition, Clk2 is downregulated in db/db mice, and reintroduction of Clk2 largely corrects glycemia. Thus, we have identified a role for and regulation of the Clk2 kinase as a component of hepatic insulin signaling and glucose metabolism.

Original languageEnglish (US)
Pages (from-to)23-34
Number of pages12
JournalCell Metabolism
Volume11
Issue number1
DOIs
StatePublished - Jan 6 2010
Externally publishedYes

Fingerprint

Gluconeogenesis
Phosphotransferases
Insulin
Liver
Glucose
Gene Expression
Protein Kinases
Insulin Resistance
Signal Transduction
Homeostasis
Down-Regulation
Food

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Cdc2-like Kinase 2 Is an Insulin-Regulated Suppressor of Hepatic Gluconeogenesis. / Rodgers, Joseph T.; Haas, Wilhelm; Gygi, Steven P.; Puigserver, Pere.

In: Cell Metabolism, Vol. 11, No. 1, 06.01.2010, p. 23-34.

Research output: Contribution to journalArticle

Rodgers, Joseph T. ; Haas, Wilhelm ; Gygi, Steven P. ; Puigserver, Pere. / Cdc2-like Kinase 2 Is an Insulin-Regulated Suppressor of Hepatic Gluconeogenesis. In: Cell Metabolism. 2010 ; Vol. 11, No. 1. pp. 23-34.
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