The kinase triad, AMPK, mTORC1 and ULK1, maintains energy and nutrient homoeostasis

Biochem Soc Trans. 2013 Aug;41(4):939-43. doi: 10.1042/BST20130030.

Abstract

In order for cells to divide in a proficient manner, they must first double their biomass, which is considered to be the main rate-limiting phase of cell proliferation. Cell growth requires an abundance of energy and biosynthetic precursors such as lipids and amino acids. Consequently, the energy and nutrient status of the cell is acutely monitored and carefully maintained. mTORC1 [mammalian (or mechanistic) target of rapamycin complex 1] is often considered to be the master regulator of cell growth that enhances cellular biomass through up-regulation of protein translation. In order for cells to control cellular homoeostasis during growth, there is close signalling interplay between mTORC1 and two other protein kinases, AMPK (AMP-activated protein kinase) and ULK1 (Unc-51-like kinase 1). This kinase triad collectively senses the energy and nutrient status of the cell and appropriately dictates whether the cell will actively favour energy- and amino-acid-consuming anabolic processes such as cellular growth, or energy- and amino-acid-generating catabolic processes such as autophagy. The present review discusses important feedback mechanisms between these three homoeostatic protein kinases that orchestrate cell growth and autophagy, with a particular focus on the mTORC1 component raptor (regulatory associated protein of mammalian target of rapamycin), as well as the autophagy-initiating kinase ULK1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenylate Kinase / metabolism*
  • Autophagy
  • Autophagy-Related Protein-1 Homolog
  • Energy Metabolism*
  • Homeostasis*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • TOR Serine-Threonine Kinases
  • Autophagy-Related Protein-1 Homolog
  • Mechanistic Target of Rapamycin Complex 1
  • Protein-Serine-Threonine Kinases
  • ULK1 protein, human
  • Adenylate Kinase