Proteomics

Dataset Information

0

SIK2 phosphorylation in response to glucagon or insulin in murine hepatocytes


ABSTRACT: The phosphorylation state of human HA-tagged-SIK2, adenovirally introduced in murine hepatocytes (C57/BL/6 strain) was analysed in unstimulated and in response to glucagon- or insulin- treated conditions. Background:- LKB1 is a master kinase that regulates metabolism and growth through AMPK and 12 other closely-related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. The salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressor downstream of LKB1 in the liver. A selective SIK inhibitor (HG-9-91-01) promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive-mutant-SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation/activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver.

INSTRUMENT(S): LTQ Orbitrap, Q TRAP

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Hepatocyte

SUBMITTER: David Campbell  

LAB HEAD: Kei Sakamoto

PROVIDER: PXD001032 | Pride | 2014-08-08

REPOSITORIES: Pride

altmetric image

Publications


LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SI  ...[more]

Similar Datasets

| E-GEOD-47179 | biostudies-arrayexpress
| E-GEOD-31638 | biostudies-arrayexpress
2020-12-01 | PXD019755 | Pride
2020-12-01 | PXD019757 | Pride
| E-GEOD-20659 | biostudies-arrayexpress
| E-GEOD-33742 | biostudies-arrayexpress
| E-MEXP-1414 | biostudies-arrayexpress
2023-07-07 | PXD012136 | Pride
2020-12-01 | PXD013478 | Pride
| E-MEXP-2636 | biostudies-arrayexpress