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Pathway

PI3K-AKT-mTOR Signaling

Human PI3K-AKT-mTOR signaling network

A growth- and nutrient-responsive network in which PI3K lipid signals regulate AKT and connect with mTORC1, metabolism, survival, and biosynthesis.

REACTOME IDENTIFIERR-HSA-1257604View source record ↗

Overview

EXPLORE BY LEVEL

Some growth signals make PI3K create PIP3, a small signal in the cell membrane. PIP3 helps bring AKT and its activating partners to the membrane. AKT can regulate mTORC1, but nutrients and energy also affect mTORC1, so the network is not a single on/off chain.

Quick Facts

AT A GLANCE
Core RelayClass I PI3K → PIP3 → AKT → TSC/RHEB → mTORC1
AKT RegulationPDPK1 and mTORC2 phosphorylate distinct AKT sites
Additional InputsAmino acids, energy status, oxygen, and growth factors regulate mTORC1
ScopeSelected human signaling network; PI3K and mTOR have additional branches and complexes

Follow the Connections

See how PI3K-AKT-mTOR Signaling links to other biological records.

Open network
Molecular complexEGFR–HER2 Heterodimersignals throughProteinEGFRparticipates inProteinHER2 (ERBB2)participates inProteinHER3 (ERBB3)participates in
All 24 Structured Connections
EGFR–HER2 Heterodimer · Molecular complexSIGNALS THROUGH →PI3K-AKT-mTOR Signaling · Pathway
EGFR · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
HER2 (ERBB2) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
HER3 (ERBB3) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
KRAS · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
p110α (PIK3CA) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
p85α (PIK3R1) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
PDK1 (PDPK1) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
AKT1 · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
AKT2 · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
GSK3β · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
FOXO1 · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
PTEN · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
TSC1 (hamartin) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
TSC2 (tuberin) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
RHEB · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
mTOR (MTOR) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
Raptor (RPTOR) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
mLST8 (MLST8) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
RICTOR · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
S6K1 (RPS6KB1) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
4E-BP1 (EIF4EBP1) · ProteinPARTICIPATES IN →PI3K-AKT-mTOR Signaling · Pathway
EGFR · ProteinSIGNALS THROUGH →PI3K-AKT-mTOR Signaling · Pathway
RAS-RAF-MEK-ERK Signaling (MAPK) · PathwayCROSSTALKS WITH →PI3K-AKT-mTOR Signaling · Pathway

Recommended Reading

Trusted references for learning more about PI3K-AKT-mTOR Signaling.

pathwayPIP3 activates AKT signaling (R-HSA-1257604)Reactome · Homo sapiens pathwayMTOR signalling (R-HSA-165159)Reactome · Homo sapiens pathwaymTORC1-mediated signalling (R-HSA-166208)Reactome · Homo sapiens pathwaySignaling by EGFR (R-HSA-177929)Reactome · Homo sapiens
Show 8 more sources
Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapyMolecular Biomedicine · 2022 · reviewSignaling by ERBB2 (R-HSA-1227986)Reactome · Homo sapiens · pathwaySignaling by Receptor Tyrosine Kinases (R-HSA-9006934)Reactome · Homo sapiens · pathwayRAF/MAP kinase cascade (R-HSA-5673001)Reactome · Homo sapiens · pathwayTranslocation of SLC2A4 (GLUT4) to the plasma membraneReactome · Homo sapiens · pathwayInsulin action at a molecular level – 100 years of progressKahn et al. · Molecular Metabolism · 2021 · reviewSignaling by insulin receptor (R-HSA-74752)Reactome · Homo sapiens · pathwayTargeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studiesSignal Transduction and Targeted Therapy · 2023 · review
Research Claims

The PI3K-AKT-mTOR label covers a network, not one linear pathway. Class I PI3K isoforms, phosphoinositide turnover, AKT isoforms, distinct mTORC1 and mTORC2 complexes, TSC-RHEB control, nutrient sensing, feedback, and receptor context all affect output. Some PI3K and mTOR functions are AKT-independent; pathway membership does not imply uniform growth or survival effects across cell types.