PI3K/AKT/mTOR - VitD3 Signalling (Homo sapiens)

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1Glycolytic enzymestranslocationComplex formationAMP/ATP ratioMitochondrial Membrane PotentialGLUT3Glucose-6-PGSK-3bROSTCA CycleCYP24A1HLA-DRALactatePyruvateAKTPFKFB4PDHA1Fructose-6-PC-MYCVDRRXRLDHACD86AMPAMPKmTOR PI3KCD80HK3Fructose Bisphosphate 1,25-(OH)2-D3TSC1C-MYCC-MYCC-MYCATPPFKFB4VDR1,25-(OH)2-D3RXRTSC2Cell cyclep65IL10IL12AATP


Pathway representation of the model proposed by Ferreira et al. in the Figure 7 C of their article: "Proposed model for the mechanism of action of 1,25(OH)2D3 in human-monocyte-derived DCs. We hypothesize that VDR-bound 1,25(OH)2D3 activates the PI3K-Akt-mTOR pathway via either forming a complex and phosphorylating the regulatory subunit of PI3K, or by other unknown mechanisms. This releases and activates the catalytic subunit, which unleashes the PI3K downstream pathway. Among other functions, activation of this pathway promotes the expression of different key glycolytic enzymes, which induces glycolysis. Control of surface marker expression and cytokine production by 1,25(OH)2D3 might arise from its impact on the PI3K pathway, which can control essential transcription factors (e.g., GSK-3β and NF-κB nuclear translocation) or from the direct regulation of transcription factors, key metabolic bifunctional enzymes, and RNA binding proteins. In the absence of glucose or glycolysis, an increase in the AMP/ATP ratio will be sensed by AMPK, which, in turn, phosphorylates TSC2 and blocks activation of the mTOR complex and its downstream processes. We further consider that the increase in OXPHOS also seen in 1,25D3-DCs is derived from the excess pyruvate generated during induced glycolysis, in addition to the control of metabolic enzymes from the oxidative branch by 1,25(OH)2D3"

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Ontology Terms



  1. Ferreira GB, Vanherwegen AS, Eelen G, Gutiérrez AC, Van Lommel L, Marchal K, Verlinden L, Verstuyf A, Nogueira T, Georgiadou M, Schuit F, Eizirik DL, Gysemans C, Carmeliet P, Overbergh L, Mathieu C; ''Vitamin D3 Induces Tolerance in Human Dendritic Cells by Activation of Intracellular Metabolic Pathways.''; Cell Rep, 2015 PubMed Europe PMC


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98518view18:52, 14 September 2018Khanspersfixed literature reference
98517view18:50, 14 September 2018KhanspersModified description
98505view12:09, 13 September 2018SusanCorrected annotation of the TCA cycle
98474view08:39, 10 September 2018SusanAdded connections
96450view09:29, 15 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
95974view10:39, 11 February 2018EgonwMetabolites don't change to genes (but this needs some redrawing anyway).
95854view17:42, 26 January 2018KhanspersModified description
95225view18:39, 26 November 2017DeSlConnected unconnected line.
95171view20:36, 20 November 2017SusanAnnotated metabolites
95170view20:33, 20 November 2017SusanAdded annotations and labels
95147view03:29, 17 November 2017AlexanderPicofixed interactions
94303view11:18, 1 September 2017Marvin M2Changed the unconnected arrows into graphical arrows
94269view12:37, 30 August 2017Madeomuga
94266view12:14, 30 August 2017MadeomugaOntology Term : 'mTOR signaling pathway' added !
94265view12:14, 30 August 2017MadeomugaOntology Term : 'phosphatidylinositol 3-kinase-Akt signaling pathway' added !
94264view12:13, 30 August 2017MadeomugaOntology Term : 'vitamin D signaling pathway' added !
94263view12:11, 30 August 2017Madeomuga
94262view12:01, 30 August 2017Madeomuga
94261view11:49, 30 August 2017MadeomugaModified description
94260view11:48, 30 August 2017Madeomuga
94259view09:49, 30 August 2017MadeomugaModified description
94258view09:48, 30 August 2017MadeomugaAdded literature and description
94257view09:21, 30 August 2017MadeomugaModified title
94256view09:19, 30 August 2017MadeomugaNew pathway

External references


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NameTypeDatabase referenceComment
1,25-(OH)2-D3MetaboliteCHEBI:17823 (ChEBI)
AKTGeneProductENSG00000142208 (Ensembl)
AMPMetaboliteHMDB03540 (HMDB)
AMPKGeneProductENSG00000162409 (Ensembl)
ATPMetaboliteCHEBI:15422 (ChEBI)
C-MYCGeneProductENSG00000136997 (Ensembl)
CD80GeneProductENSG00000121594 (Ensembl)
CD86GeneProductENSG00000114013 (Ensembl)
CYP24A1GeneProductENSG00000019186 (Ensembl)
Cell cyclePathwayWP179 (WikiPathways)
Fructose Bisphosphate MetaboliteCHEBI:65056 (ChEBI)
Fructose-6-PMetaboliteCHEBI:16084 (ChEBI)
GLUT3GeneProductENSG00000059804 (Ensembl)
GSK-3bGeneProductENSG00000082701 (Ensembl)
Glucose-6-PMetaboliteCHEBI:4170 (ChEBI)
HK3GeneProductENSG00000160883 (Ensembl)
HLA-DRAGeneProductENSG00000204287 (Ensembl)
IL10GeneProductENSG00000136634 (Ensembl)
IL12AGeneProductENSG00000168811 (Ensembl)
LDHAGeneProductENSG00000134333 (Ensembl)
LactateMetaboliteCHEBI:24996 (ChEBI)
PDHA1GeneProductENSG00000131828 (Ensembl)
PFKFB4GeneProductENSG00000114268 (Ensembl)
PI3KGeneProductENSG00000121879 (Ensembl)
PyruvateMetaboliteCHEBI:15361 (ChEBI)
ROSMetaboliteQ424361 (Wikidata) Reactive oxygen species
RXRGeneProductENSG00000186350 (Ensembl)
TCA CyclePathwayWP999 (WikiPathways)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
VDRGeneProductENSG00000111424 (Ensembl)
mTOR GeneProductENSG00000198793 (Ensembl)
p65GeneProductENSG00000173039 (Ensembl)

Annotated Interactions

No annotated interactions

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