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MTOR — ULK1
Pathways - manually collected, often from reviews:
-
KEGG mTOR signaling pathway:
MTOR
→
ULK1/ULK2/ULK3
(protein-protein, inhibition)
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
mTORC1/ULK1-2/ATG13/FIP200 complex (MTOR-MLST8-RPTOR-ULK1_ULK2-ATG13-RB1CC1)
(modification, collaborate)
Hosokawa et al., Mol Biol Cell 2009, Jung et al., Mol Biol Cell 2009, Ganley et al., J Biol Chem 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1 complex (MTOR-MLST8-RPTOR)
→
ULK1-2/ATG13/FIP200 complex (ULK1_ULK2-ATG13-RB1CC1)
(modification, collaborate)
Hosokawa et al., Mol Biol Cell 2009, Jung et al., Mol Biol Cell 2009, Ganley et al., J Biol Chem 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC1/ULK1-2/ATG13/FIP200 complex (MTOR-MLST8-RPTOR-ULK1_ULK2-ATG13-RB1CC1)
→
ULK1-2/ATG13/FIP200 complex (ULK1_ULK2-ATG13-RB1CC1)
(modification, collaborate)
Hosokawa et al., Mol Biol Cell 2009, Jung et al., Mol Biol Cell 2009, Ganley et al., J Biol Chem 2009
Evidence: mutant phenotype, assay, physical interaction
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
MLST8/MTOR/RPTOR
→
ULK1
(inhibition)
-
WikiPathways PI3K-AKT-mTOR signaling pathway and therapeutic opportunities:
Complex of RPTOR-MTOR
→
Complex of RB1CC1-ULK1-ATG13
(activation)
-
WikiPathways Senescence and Autophagy in Cancer:
MTOR
→
ULK1
(inhibition)
-
WikiPathways Target Of Rapamycin (TOR) Signaling:
Complex of RPTOR-MLST8-MTOR
→
ULK1
(inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Jung et al., Mol Biol Cell 2009
:
ULK-Atg13-FIP200 complexes
mediate mTOR signaling to the autophagy machinery ... Inhibition of
mTOR by rapamycin or leucine deprivation, the conditions that induce autophagy, leads to dephosphorylation of ULK1, ULK2, and Atg13 and
activates ULK to phosphorylate FIP200 ... These findings demonstrate that the
ULK-Atg13-FIP200 complexes are direct targets of mTOR and important regulators of autophagy in
response to
mTOR signaling
Lee et al., PloS one 2010
:
Taken together, these results suggest that AMPK association with ULK1 plays an important role in autophagy induction, at least in part, by phosphorylation of raptor to lift the inhibitory
effect of
mTOR on the
ULK1 autophagic complex
Dunlop et al., Autophagy 2011
:
ULK1 inhibits
mTORC1 signaling, promotes multisite Raptor phosphorylation and hinders substrate binding ... Interestingly,
ULK1 overexpression also increases phosphorylation of Raptor Ser863 and the mTOR autophosphorylation site, Ser2481 in a
mTORC1 dependent manner ... Interestingly,
ULK1 overexpression also increases phosphorylation of Raptor Ser863 and the mTOR autophosphorylation site, Ser2481 in a
mTORC1 dependent manner ... We propose a new mechanism whereby
ULK1 contributes to
mTORC1 inhibition through hindrance of substrate docking to Raptor
Shang et al., Autophagy 2011
:
These studies show that both
mTOR and AMPK directly
regulate Ulk1 and coordinate the mammalian autophagy initiation
Jung et al., Autophagy 2011
:
ULK1 inhibits the kinase activity of
mTORC1 and cell proliferation ... ( 1-3 ) Here, we investigated how ULK1 regulates mTORC1 signaling, and found that
ULK1 inhibits the kinase activity of
mTORC1 and cell proliferation ... Deficiency or knockdown of ULK1 or its homolog ULK2
enhanced mTORC1 signaling, cell proliferation rates and accumulation of cell mass, whereas overexpression of
ULK1 had the opposite effect ... In addition,
ULK1 was found to bind raptor, induce its phosphorylation, and
inhibit the kinase activity of
mTORC1 ... In addition,
ULK1 was found to bind raptor, induce its phosphorylation, and
inhibit the kinase activity of
mTORC1 ... These results demonstrate that
ULK1 negatively
regulates the kinase activity of
mTORC1 and cell proliferation in a manner independent of Atg5 and TSC2
Castets et al., Cell Metab 2013
:
In young TSCmKO mice, constitutive and starvation induced autophagy is blocked at the induction steps via
mTORC1 mediated inhibition of
Ulk1 , despite FoxO3 activation