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Details on Person One of the two functional complexes formed by mTOR kinase is...

Class:IdSummation:166182
_displayNameOne of the two functional complexes formed by mTOR kinase is...
_timestamp2026-02-02 11:48:41
created[InstanceEdit:166183] de Bono, B, 2005-08-22 12:07:37
literatureReference[LiteratureReference:5672799] Mammalian target of rapamycin complex 1-mediated phosphorylation of eukaryotic initiation factor 4E-binding protein 1 requires multiple protein-protein interactions for substrate recognition
[LiteratureReference:376999] Rheb binds and regulates the mTOR kinase
[LiteratureReference:5655438] Growing roles for the mTOR pathway
[LiteratureReference:5672795] mTOR signaling at a glance
[LiteratureReference:377264] PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase
[LiteratureReference:5672813] mTORC1 signaling: what we still don't know
[LiteratureReference:165687] Raptor, a binding partner of target of rapamycin (TOR), mediates TOR
[LiteratureReference:165681] Signaling by target of rapamycin proteins in cell growth control
[LiteratureReference:5672785] Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor
[LiteratureReference:5672818] Identification of novel single amino acid changes that result in hyperactivation of the unique GTPase, Rheb, in fission yeast
[LiteratureReference:5672792] mTORC1 signalling and mRNA translation
[LiteratureReference:5672805] Regulation of translation initiation in eukaryotes: mechanisms and biological targets
[LiteratureReference:5672807] Where is mTOR and what is it doing there?
modified[InstanceEdit:5655428] Jupe, Steve, 2014-12-05
[InstanceEdit:5672806] Jupe, Steve, 2015-02-06
[InstanceEdit:5687546] Jupe, Steve, 2015-04-08
[InstanceEdit:5693184] Jupe, Steve, 2015-05-14
[InstanceEdit:8865030] D'Eustachio, Peter, 2016-03-18
[InstanceEdit:9980587] Orlic-Milacic, Marija, 2026-01-30
[InstanceEdit:9980735] Orlic-Milacic, Marija, 2026-02-02
textOne of the two functional complexes formed by mTOR kinase is mTORC1 (mammalian TOR complex 1), which consists of MTOR, and at least two other proteins: RPTOR (Raptor, Regulated Associated Protein of mTOR) and MLST8. RPTOR serves as a scaffolding protein to bridge the interaction between mTOR and its substrates, defining the substrate specificity of mTORC1 (Dunlop et al. 2008). MLST8 enhances the association of mTOR with RPTOR. The complex is activated by association with RHEB, a small guanosine triphosphate (GTP)-binding protein that potently activates the protein kinase activity of mTORC1 in vivo (Long et al. 2005, Sarbassov et al. 2005) and in vitro (Sancak et al. 2007). Rheb interacts with and activates mTORC1 (reviewed in Laplante & Sabatini 2009, Wang & Proud 2011) and is necessary for the activation of mTORC1 by all signals. Besides binding directly to mTOR, RHEB can bind RPTOR and MLST8 (Hara et al. 2002, Inoki et al. 2005). RHEB-GTP charging does not promote the RHEB:mTOR interaction, but GTP-charged RHEB is required for activation of mTOR catalytic activity (Avruch et al. 2009). Studies in fission yeast strongly suggest that RHEB must bind mTOR for activation of catalytic activity (Urano et al. 2005) and this has also been demonstrated in mammals (Sancak et al. 2007) though this has been questioned (Wang & Proud 2011). It is unclear whether active mTORC1 remains bound to Rheb or, alternatively, once activated, can dissociate from Rheb. mTORC1 activity has been reported at many cellular localizations but some of these reports may be identifying mTOR as part of mTORC2. mTORC1 is predominantly lysosomal, though under amino acid starvation conditions it exhibits a diffuse, cytoplasmic distribution. It may have different functions when active in the cytoplasm. mTORC1 associates with the general translation initiation complex eIF3 and phosphorylates the translation inhibitor 4E-BP upon stimulation by growth factors and nutrients, promoting translation initiation (Proud 2009, Sonenberg & Hinnebusch 2009). These events presumably take place in the cytoplasm (Betz & Hall 2013).
(summation)[Reaction:165680] Formation of active mTORC1 complex [Homo sapiens]
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