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Signaling crosstalk between the mTOR complexes

Jianling Xie1, Chris G Proud1

  • 1Centre for Biological Sciences; University of Southampton; Southampton, UK.

Translation (Austin, Tex.)
|January 19, 2016
PubMed

Insights

The mechanistic target of rapamycin (mTOR) pathway involves two complexes, mTORC1 and mTORC2, that regulate cell growth. Recent findings reveal intricate crosstalk between these complexes, impacting human diseases and drug resistance.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The mechanistic target of rapamycin (mTOR) is a key protein kinase regulating cellular anabolic processes like protein synthesis.
  • mTOR exists in two distinct multi-protein complexes, mTORC1 and mTORC2, each with unique targets and functions.
  • While sensitive to rapamycin differently, mTORC1 and mTORC2 share upstream regulators and exhibit linked activation patterns.

Purpose of the Study:

  • To summarize recently discovered features of crosstalk between mTORC1 and mTORC2.
  • To discuss the implications of aberrant mTOR complex crosstalk in human diseases.
  • To explore the role of mTOR complex crosstalk in the development of drug resistance.

Main Methods:

  • Literature review of recent studies on mTORC1 and mTORC2 signaling.
  • Analysis of shared upstream signaling molecules (e.g., PI3K, TSC).
  • Examination of feedback mechanisms influencing mTOR complex activation.

Main Results:

  • mTORC1 and mTORC2, despite functional differences, are tightly regulated and interconnected.
  • Shared signaling pathways and feedback loops demonstrate complex crosstalk.
  • Aberrant crosstalk contributes to disease pathogenesis and therapeutic resistance.

Conclusions:

  • Understanding mTORC1/mTORC2 crosstalk is crucial for deciphering cellular regulation.
  • Dysregulated mTOR signaling pathways offer potential therapeutic targets.
  • Further research into mTOR complex interactions may yield novel strategies for disease treatment and overcoming drug resistance.
Keywords:
SIN1TSC2mRNA translationmTORC1mTORC2protein synthesis

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