Lipin-1 is a novel substrate of protein phosphatase PGAM5

Biochem Biophys Res Commun. 2019 Feb 19;509(4):886-891. doi: 10.1016/j.bbrc.2019.01.031. Epub 2019 Jan 11.

Abstract

Lipin-1 has multiple functions that regulate lipid and energy metabolism according to its subcellular localization. The subcellular localization of Lipin-1 is determined by kinase-dependent phosphorylation; however, the phosphatase that dephosphorylates and inactivates Lipin-1 has remained elusive. Using an immunoprecipitation and LC-MS/MS approach we have identified phosphoglycerate mutase family member 5 (PGAM5), a serine/threonine specific protein phosphatase, as a regulator of Lipin-1 activity. Treatment of human hepatocellular carcinoma cells with carbonyl cyanide m-chlorophenyl hydrazone (CCCP), which activates endogenous PGAM5, promoted dephosphorylation and nuclear accumulation of Lipin-1. Our findings further elucidate the molecular mechanisms that regulate Lipin-1.

Keywords: Dephosphorylation; Lipid metabolism; Lipin-1; PGAM5; Phosphatase; Subcellular localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Carcinoma, Hepatocellular / metabolism
  • Humans
  • Lipid Metabolism
  • Liver Neoplasms / metabolism
  • Mitochondrial Proteins / metabolism*
  • Phosphatidate Phosphatase / metabolism*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Protein Binding
  • Tumor Cells, Cultured

Substances

  • Mitochondrial Proteins
  • PGAM5 protein, human
  • Phosphoprotein Phosphatases
  • LPIN1 protein, human
  • Phosphatidate Phosphatase