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Interactive Pathways & Processes

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mTOR Signaling Pathway

Click on one of the choices in the Explore Pathways box to highlight the molecules involved in each cellular process and how they interact with mTOR.

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TNF-alpha

TNF R

RIP1

NIK

IKK beta

REDD1

p53

AMPK

MO25

LKB1

STRAD

GSK-3beta

APC

Axin

CK1

Dishevelled

LRP-5/6

Frizzled

Wnt

R-Spondin

HSPG

Lgr4,5,6

Growth Factor Receptors

Ras

PI 3-K

PIP₂

PIP₃

PTEN

Growth Factors

GRB2

SOS

IRS1

Raf

MEK1/2

ERK1/2

Akt

PDK-1

RSK

TSC1/2

TBC
1D7

Rheb

DEPTOR

GBL

Raptor

PRAS40

mTOR

MTORC1

Lysosome

DEPTOR

mSIN1

mTOR

Proctor

Rictor

GBL

MTORC2

SGK1

PKC alpha

Rho

Rac1

Paxillin

p70 S6 Kinase

eEF2K

eEF2

Lipin 1

Inactive
SREBP1/2

Active
SREBP1/2

SREBP1/2

eIF4B

PDCD4

4EBP1

eIF4A

eIF4G

eIF4E

Maf1

TIF1A

Pol I

Pol III

Hypoxia

DNA Damage

Energy Stress

Protein
Elongation

Lysosome
Biogenesis

Megabolism

Autophagy

Translation
Initiation

Cytoskeletal
Rearrangement

Fatty Acid and Cholesterol
Synthesis Genes

rRNA

tRNA

Overview of mTOR Signaling

The mammalian Target of Rapamycin (mTOR) Complex is the central cellular regulator of anabolic and catabolic cellular metabolism and survival. mTOR forms at least two distinct multi-protein complexes (mTORCs) with additional regulatory proteins. mTORC1 includes mTOR, Raptor, Pras40, Deptor, and GBL/mLST8 while mTORC2 includes mTOR, Rictor, mSin1, Proctor/PRR5, Deptor, and GBL/mLST8. mTOR activity is regulated in response to both extracellular and intracellular cues. Extracellular signaling factors, including Wnts, TNF-alpha, and growth factors, signal through a variety of intracellular pathways to TSC1/2, to regulate mTORC1 activity. In addition to responding to extracellular cues, mTORC1 activity is also regulated by intracellular cues including energy availability, oxygen levels, and amino acid availability. In the presence of available amino acids, the mTOR Complex 1 (mTORC1) is recruited to the lysosomal membrane where it initiates anabolic activities including protein synthesis, lipid synthesis, autophagy, and mitochondrial metabolism and biogenesis.

Less is known about the upstream signals and cellular functions that regulate mTORC2. mTORC2 activity is strongly correlated with AKT activity. mTORC2 has been shown to regulate cytoskeletal rearrangement, as well as cell survival and proliferation.

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