The mTORC2 signaling network: targets and cross-talks

Area of Science:

• Cellular Biology
• Molecular Signaling
• Metabolism

Background:

• The mechanistic target of rapamycin (mTOR) pathway is crucial for cell metabolism, growth, and survival.
• mTOR functions via two complexes: mTORC1, targeted by rapamycin, and mTORC2, less understood but activated by growth and stress signals.

Approach:

• This review synthesizes current knowledge on mTORC2 regulation by cellular stimuli.
• It examines mTORC2's role in mediating signals from growth factor and G-protein coupled receptors.
• The review discusses how stress conditions impact mTORC2 activation and metabolic reprogramming.

Key Points:

• mTORC2 signaling is modulated by compartmentalization and complex component changes.
• Key substrates include AGC kinases like Akt, PKC, and SGK, mediating functions in growth, proliferation, survival, and differentiation.
• Cross-talk with other signaling and metabolic pathways influences mTORC2's cellular output.

Conclusions:

• Understanding mTORC2 regulation and function is critical for deciphering its role in cell survival and metabolic adaptation.
• Targeting the mTORC2 pathway holds therapeutic promise for diseases with deregulated mTOR signaling.