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Signal Transduction
Eukaryotes
PI3K/AKT/mTOR Pathway
Regulates cell survival, growth, and metabolism via phosphoinositide signaling.
Overview
The PI3K/AKT/mTOR pathway is activated by receptor tyrosine kinases, G-protein coupled receptors, and integrins. PI3K generates PIP3, which recruits AKT to the membrane for activation. Active AKT phosphorylates numerous downstream targets including mTOR, BAD, GSK-3β, and FOXO transcription factors, promoting cell survival, growth, proliferation, and metabolic regulation. PTEN serves as a major negative regulator by dephosphorylating PIP3.
Cellular Location
Cytoplasm, membrane
Clinical Significance
Frequently hyperactivated in cancer; PTEN is one of the most commonly lost tumor suppressors; target of rapamycin and PI3K inhibitors.