Related Experiment Video

Updated: May 7, 2026

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)

Dudley W Lamming1, Gokhan Demirkan, Joan M Boylan

  • 13Division of Pediatric Endocrinology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA. philip_gruppuso@brown.edu.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|September 28, 2013
PubMed

Insights

Hepatic mechanistic target of rapamycin complex 2 (mTORC2) regulates metabolism and cell growth. This study reveals mTORC2

Area of Science:

  • Cell Biology
  • Metabolism
  • Molecular Biology

Background:

  • The mechanistic target of rapamycin (mTOR) pathway, crucial for cell growth and metabolism, comprises two complexes: mTORC1 and mTORC2.
  • While mTORC1 is well-characterized, the physiological functions of mTORC2, particularly in the liver, remain largely unknown.

Purpose of the Study:

  • To elucidate the role of hepatic mTORC2 in regulating cellular processes and metabolism in vivo.
  • To identify specific molecular networks controlled by mTORC2 in liver cells.

Main Methods:

  • Utilized Rictor-knockout (RKO) mice with liver-specific deletion of an mTORC2 component.
  • Employed genomic and phosphoproteomic analyses following a food withdrawal/refeeding paradigm to activate mTOR signaling.
  • Administered rapamycin to differentiate mTORC2-specific effects.

Main Results:

  • Hepatic mTORC2 was found to regulate a complex network of gene expression and post-translational modifications impacting intermediary metabolism, ribosomal biogenesis, and proteasomal biogenesis.
  • Observed cell-autonomous effects of mTORC2 signaling on metabolic gene regulation in cultured fetal hepatocytes.
  • Identified mTORC2-dependent signaling to 144 proteins, including metabolic enzymes and regulators, and a reduction in p38 MAPK signaling.

Conclusions:

  • Hepatic mTORC2 plays a broad role in regulating fundamental biological processes under physiological conditions.
  • Findings provide a foundation for developing targeted therapies aimed at modulating mTORC2 signaling for metabolic and cellular regulation.
Keywords:
gene expressionlivermetabolismproteomicssignal transduction

More Related Videos

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...