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MTOR — PRR5
Pathways - manually collected, often from reviews:
-
NCI Pathway Database mTOR signaling pathway:
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
→
PKC alpha (PRKCA)
(regulation of protein stability, activates)
Ikenoue et al., EMBO J 2008
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
DEPTOR (DEPTOR)
→
mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5)
(modification, collaborate)
Huang et al., Mol Cell Biol 2008, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
DEPTOR (DEPTOR)
→
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
(modification, collaborate)
Huang et al., Mol Cell Biol 2008, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5)
→
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
(modification, collaborate)
Huang et al., Mol Cell Biol 2008, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5)
→
TSC1/TSC2 complex (TSC1-TSC2)
(modification, collaborate)
Huang et al., Mol Cell Biol 2008, Peterson et al., Cell 2009
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
RAC1/GTP complex (RAC1)
→
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
(regulation of actin cytoskeleton organization, collaborate)
Sarbassov et al., Curr Biol 2004, Jacinto et al., Nat Cell Biol 2004
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
→
Paxillin (PXN)
(regulation of actin cytoskeleton organization, activates)
Sarbassov et al., Curr Biol 2004, Jacinto et al., Nat Cell Biol 2004
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
→
RHOA/GTP complex (RHOA)
(regulation of actin cytoskeleton organization, activates)
Sarbassov et al., Curr Biol 2004, Jacinto et al., Nat Cell Biol 2004
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
RICTOR (RICTOR)
→
mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
RICTOR (RICTOR)
→
mTOR/GBL/SIN1/PROTOR1/DEPTOR complex (MTOR-MLST8-DEPTOR-MAPKAP1-PRR5)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC2/DEPTOR complex (MTOR-MLST8-MAPKAP1-DEPTOR-RICTOR-PRR5)
→
mTOR/GBL/SIN1/PROTOR1/DEPTOR complex (MTOR-MLST8-DEPTOR-MAPKAP1-PRR5)
(modification, collaborate)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
None
→
mTOR/GBL/SIN1/PROTOR1/DEPTOR complex (MTOR-MLST8-DEPTOR-MAPKAP1-PRR5)
(modification, activates)
Fang et al., Science 2001, Toschi et al., Mol Cell Biol 2009
Evidence: mutant phenotype, physical interaction
-
NCI Pathway Database mTOR signaling pathway:
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
→
PKC alpha (PRKCA)
(modification, activates)
Sarbassov et al., Curr Biol 2004, Guertin et al., Dev Cell 2006, Ikenoue et al., EMBO J 2008
Evidence: mutant phenotype
-
NCI Pathway Database mTOR signaling pathway:
mTORC2 complex (MTOR-MLST8-RICTOR-MAPKAP1-PRR5)
→
AKT1 (AKT1)
(modification, activates)
Sarbassov et al., Science 2005, Frias et al., Curr Biol 2006, Jacinto et al., Cell 2006, Yang et al., Genes Dev 2006, Guertin et al., Dev Cell 2006, Pearce et al., Biochem J 2007, Woo et al., J Biol Chem 2007, Huang et al., Mol Cell Biol 2008, Ikenoue et al., EMBO J 2008
Evidence: mutant phenotype, assay, physical interaction
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
PRR5
—
MTOR
(physical association, affinity chromatography technology)
Martin et al., Biochem Biophys Res Commun 2008
-
IRef Biogrid Interaction:
PRR5
—
MTOR
(physical association, affinity chromatography technology)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of 27 proteins
(association, anti bait coimmunoprecipitation)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of 13 proteins
(association, anti tag coimmunoprecipitation)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of PRR5-MTOR-YWHAE-YWHAB-HSPA1A-MLST8-RICTOR
(association, tandem affinity purification)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of RPTOR-MAPKAP1-MTOR-MLST8-PRR5-RICTOR
(association, anti bait coimmunoprecipitation)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of 41 proteins
(association, anti bait coimmunoprecipitation)
Pearce et al., Biochem J 2007
-
IRef Intact Interaction:
Complex of RICTOR-PRR5-MTOR-MAPKAP1-MLST8
(association, anti tag coimmunoprecipitation)
Pearce et al., Biochem J 2007
Text-mined interactions from Literome
Guertin et al., Dev Cell 2006
:
Thus, mTORC1 function is essential in early development,
mLST8 is
required only for
mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKCalpha pathways
Woo et al., J Biol Chem 2007
(Breast Neoplasms...) :
PRR5 interacts with rictor, but not raptor, and the interaction is
independent of
mTOR and not disturbed under conditions that disrupt the mTOR-rictor interaction
Huang et al., Mol Cell Biol 2008
:
However, how
mTORC2 is regulated and whether the
TSC1-TSC2 complex is
involved are unknown
Wang et al., Oncogene 2008
(Prostatic Neoplasms) :
Inhibition of both mTORC1 and
mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity
resulted from the inhibition of mTORC1, but not
mTORC2 ... Inhibition of both mTORC1 and
mTORC2 by rapamycin induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity
resulted from the inhibition of
mTORC1 , but not mTORC2
Partovian et al., Mol Cell 2008
:
Reduced
mTORC2 activity in S4 ( -/- ) endothelial cells
results in decreased
FoxO1/3a and eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice ... Reduced
mTORC2 activity in S4 ( -/- ) endothelial cells
results in decreased FoxO1/3a and
eNOS phosphorylation, decreased endothelial cell size, and increased arterial blood pressure in S4 ( -/- ) mice
Bozulic et al., Curr Opin Cell Biol 2009
(Neoplasms) :
This present review concerns
PKB regulation by
mTORC2 and DNA-PK in a stimulus dependent and context dependent manner and the possible implications of this for PKB activity, substrate specificity and therapeutic intervention
Cybulski et al., Proc Natl Acad Sci U S A 2009
(Fatty Liver) :
mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is
activated by
insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB ...
mTORC2 , which consists of rictor, mSIN1, mLST8, and mTOR, is
activated by
insulin/IGF1 and phosphorylates Ser-473 in the hydrophobic motif of Akt/PKB
Kim et al., J Biol Chem 2010
(Breast Neoplasms...) :
In contrast,
API-1 had no effects on the activities of the upstream Akt activators, phosphatidylinositol 3-kinase, phosphatidylinositol dependent kinase-1, and
mTORC2
Lyo et al., Biochem Biophys Res Commun 2010
(Kidney Neoplasms) :
We report here that the PLD/mTOR dependent stabilization of
HDM2 involves
mTORC2 and the AGC family kinase serum- and glucocorticoid-inducible kinase 1 ( SGK1 )
Chen et al., Mol Carcinog 2010
(Neoplasms) :
In this report, we focused on studying the
role of mTORC1 and
mTORC2 in rapamycin mediated Akt and
ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... In this report, we focused on studying the
role of mTORC1 and
mTORC2 in rapamycin mediated
Akt and ERK phosphorylation, and the antitumor effect of rapamycin in cancer cells in combination with Akt and ERK inhibitors ... Collectively, we conclude that
mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of Akt and
ERK , and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells ... Collectively, we conclude that
mTORC2 plays a much more important role than mTORC1 in rapamycin mediated phosphorylation of
Akt and ERK, and cotargeting AKT and ERK signaling may be a new strategy for enhancing the efficacy of rapamycin based therapeutic approaches in cancer cells
Lee et al., Immunity 2010
:
mTORC2 promoted phosphorylation of
protein kinase B ( PKB, or Akt ) and PKC, Akt activity, and nuclear NF-kappaB transcription factors in response to T cell activation
Gulhati et al., Cancer Res 2011
(Colorectal Neoplasms...) :
mTORC1 and
mTORC2 regulate
EMT , motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways
Goncharova et al., Mol Cell Biol 2011
:
Our data demonstrate that
mTORC2 dependent activation of
RhoA is required for TSC2-null cell growth and survival and suggest that targeting both mTORC2 and mTORC1 by a combination of proapoptotic simvastatin and cytostatic rapamycin shows promise for combinational therapeutic intervention in diseases with TSC2 dysfunction
Zhao et al., Mol Cell 2011
:
DEPTOR , an
inhibitor of mTORC1 and
mTORC2 , is degraded via ubiquitin-proteasome pathway by an unknown E3 ubiquitin ligase
Gupta et al., Blood 2012
(Lymphoma) :
Dual
mTORC1/mTORC2 inhibition
diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
Glidden et al., J Biol Chem 2012
:
Although
Rictor is
required for the stability and activity of
mTORC2 , little is known about functional regions or post-translational modifications within Rictor that are responsible for regulating mTORC2
Rodrik-Outmezguine et al., Cancer Discov 2011
:
Inhibition of
mTORC2 leads to AKT serine 473 ( S473 ) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and
AKT signaling
Espona-Fiedler et al., Biochem Pharmacol 2012
(Melanoma) :
The inhibition of mTORC1 and
mTORC2 complexes by PG or OBX
resulted in a loss of
AKT phosphorylation at S473, preventing its full activation, with no significant effect on T308
Zhang et al., Proc Natl Acad Sci U S A 2012
:
Taken together, these data reveal a signaling pathway by which phosphatidic acid synthesized via the glycerol-3-phosphate pathway
inhibits mTORC2 activity by decreasing the association of rictor and
mTOR , thereby down regulating insulin action
Zhao et al., Neoplasia (New York, N.Y.) 2012
(Neoplasms) :
Recently, we and others found that
DEPTOR , a naturally occurring
inhibitor of both mTORC1 and
mTORC2 , was degraded by SCF ( Skp1-Cullin-F box proteins ) E3 ubiquitin ligase, the founding member of cullin-RING-ligases ( CRLs ), resulting in mTOR activation and cell proliferation
Ju et al., Cell Signal 2013
:
We have previously demonstrated that
syndecan 4 (S4) regulates the intracellular localization of
mTORC2 , thus altering phosphorylation of Akt at serine473 ( Ser473 ), one of two critical phosphorylation sites essential for the full activation of Akt [1 ]
Le Bacquer et al., J Endocrinol 2013
(Hyperglycemia) :
mTORC1 and
mTORC2 regulate
insulin secretion through Akt in INS-1 cells
Maru et al., J Urol 2013
(Carcinoma, Renal Cell...) :
Results show that
mTORC2 might
regulate E-cadherin expression and suppress cell motility by controlling the mTORC2-HIF-2a signaling pathway
Chen et al., J Invest Dermatol 2013
(Psoriasis) :
mTORC2-PKBa/Akt1 Serine 473 Phosphorylation Axis Is
Essential for Regulation of
FOXP3 Stability by Chemokine CCL3 in Psoriasis
Razmara et al., Cell communication and signaling : CCS 2013
:
Thus, whereas both mTORC1 and
mTORC2 are activated in a
PI3K dependent manner, different additional signaling pathways are needed
Shortt et al., Blood 2013
(Lymphoma, B-Cell) :
Moreover, apoptosis was initiated at drug concentrations insufficient to antagonize
PI3K/mTORC2 regulated
AKT phosphorylation
Jeon et al., Biochim Biophys Acta 2013
(Breast Neoplasms...) :
When SelW was down-regulated,
mTORC2 dependent phosphorylation of
Akt at Ser473 was decreased
Melnik et al., Exp Dermatol 2013
:
Antiandrogens may attenuate mTORC1 by suppressing
mTORC2 mediated
Akt/TSC2 signalling ... Antiandrogens may attenuate mTORC1 by suppressing
mTORC2 mediated
Akt/TSC2 signalling