Role of mTOR1 and mTOR2 complexes in MEG-01 cell physiology

Thromb Haemost. 2015 Nov;114(5):969-81. doi: 10.1160/TH14-09-0727. Epub 2015 Jul 23.

Abstract

The function of the mammalian target of rapamycin (mTOR) is upregulated in response to cell stimulation with growing and differentiating factors. Active mTOR controls cell proliferation, differentiation and death. Since mTOR associates with different proteins to form two functional macromolecular complexes, we aimed to investigate the role of the mTOR1 and mTOR2 complexes in MEG-01 cell physiology in response to thrombopoietin (TPO). By using mTOR antagonists and overexpressing FKBP38, we have explored the role of both mTOR complexes in proliferation, apoptosis, maturation-like mechanisms, endoplasmic reticulum-stress and the intracellular location of both active mTOR complexes during MEG-01 cell stimulation with TPO. The results demonstrate that mTOR1 and mTOR2 complexes play different roles in the physiology of MEG-01 cells and in the maturation-like mechanisms; hence, these findings might help to understand the mechanism underlying generation of platelets.

Keywords: MEG-01 cells; apoptosis; calcium homeostasis; mTOR; rapamycin; raptor; rictor; torin1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • Megakaryocyte Progenitor Cells / drug effects
  • Megakaryocyte Progenitor Cells / physiology*
  • Multiprotein Complexes / metabolism*
  • Naphthyridines / pharmacology
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism*
  • Tacrolimus Binding Protein 1A / genetics
  • Tacrolimus Binding Protein 1A / metabolism
  • Tacrolimus Binding Proteins / genetics
  • Tacrolimus Binding Proteins / metabolism
  • Thrombopoietin / metabolism
  • Transgenes / genetics

Substances

  • 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one
  • FKBP8 protein, human
  • Multiprotein Complexes
  • Naphthyridines
  • Thrombopoietin
  • Mechanistic Target of Rapamycin Complex 1
  • Mechanistic Target of Rapamycin Complex 2
  • TOR Serine-Threonine Kinases
  • Tacrolimus Binding Protein 1A
  • Tacrolimus Binding Proteins
  • Sirolimus