RGD Reference Report - Regulation of mTORC1 by PI3K signaling. - Rat Genome Database

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Regulation of mTORC1 by PI3K signaling.

Authors: Dibble, CC  Cantley, LC 
Citation: Dibble CC and Cantley LC, Trends Cell Biol. 2015 Sep;25(9):545-55. doi: 10.1016/j.tcb.2015.06.002. Epub 2015 Jul 6.
RGD ID: 11535034
Pubmed: PMID:26159692   (View Abstract at PubMed)
PMCID: PMC4734635   (View Article at PubMed Central)
DOI: DOI:10.1016/j.tcb.2015.06.002   (Journal Full-text)

The class I phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling network directs cellular metabolism and growth. Activation of mTORC1 [composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8(mLST8), 40-kDa proline-rich Akt substrate (PRAS40), and DEP domain-containing mTOR-interacting protein (DEPTOR)] depends on the Ras-related GTPases (Rags) and Ras homolog enriched in brain (Rheb) GTPase and requires signals from amino acids, glucose, oxygen, energy (ATP), and growth factors (including cytokines and hormones such as insulin). Here we discuss the signal transduction mechanisms through which growth factor-responsive PI3K signaling activates mTORC1. We focus on how PI3K-dependent activation of Akt and spatial regulation of the tuberous sclerosis complex (TSC) complex (TSC complex) [composed of TSC1, TSC2, and Tre2-Bub2-Cdc16-1 domain family member 7 (TBC1D7)] switches on Rheb at the lysosome, where mTORC1 is activated. Integration of PI3K- and amino acid-dependent signals upstream of mTORC1 at the lysosome is detailed in a working model. A coherent understanding of the PI3K-mTORC1 network is imperative as its dysregulation has been implicated in diverse pathologies including cancer, diabetes, autism, and aging.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Rheb  (Ras homolog, mTORC1 binding)
Tbc1d7  (TBC1 domain family, member 7)
Tsc1  (TSC complex subunit 1)
Tsc2  (TSC complex subunit 2)

Genes (Mus musculus)
Rheb  (Ras homolog enriched in brain)
Tbc1d7  (TBC1 domain family, member 7)
Tsc1  (TSC complex subunit 1)
Tsc2  (TSC complex subunit 2)

Genes (Homo sapiens)
RHEB  (Ras homolog, mTORC1 binding)
TBC1D7  (TBC1 domain family member 7)
TSC1  (TSC complex subunit 1)
TSC2  (TSC complex subunit 2)


Additional Information