◀ Back to AKT1
AKT1 — TSC1
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
Complex of TSC1-TSC2
→
AKT1
(decreases, AKT1 Activity, TSC1/TSC2 Activity)
Petroulakis et al., Br J Cancer 2006*
Evidence: In turn, Akt phosphorylates the tuberous scleorisis complex, TSC1/TSC2 (hamartin/tuberin) that serves as a GTPase activating protein (GAP) for the small G protein, Ras homolog enriched in brain (Rheb).
-
NCI Pathway Database mTOR signaling pathway:
AKT1 (AKT1)
→
TSC1/TSC2 complex (TSC1-TSC2)
(modification, activates)
Inoki et al., Nat Cell Biol 2002*, Garami et al., Mol Cell 2003, Sancak et al., Mol Cell 2007
Evidence: mutant phenotype, assay, physical interaction
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
AKT1/AKT3/AKT2
→
TSC1/TSC2
(inhibition)
-
WikiPathways Angiopoietin Like Protein 8 Regulatory Pathway:
AKT1/AKT2
→
TSC2/TSC1
(inhibition)
Kwiatkowski et al., Hum Mol Genet 2005*, Vadlakonda et al., Frontiers in oncology 2013*
-
WikiPathways Insulin Signaling:
GSK3B/AKT2/AKT1/SGK3/SGK1/GSK3A/PDPK1/SGK2
→
TSC2/TSC1
(inhibition)
-
WikiPathways Angiopoietin Like Protein 8 Regulatory Pathway:
AKT1/AKT2
→
TSC2/TSC1
(inhibition)
-
WikiPathways Signaling Pathways in Glioblastoma:
AKT1/AKT2/AKT3
→
Complex of TSC1-TSC2
(mim-inhibition)
-
WikiPathways Target Of Rapamycin (TOR) Signaling:
AKT1
→
Complex of TSC2-TSC1
(inhibition)
-
WikiPathways BDNF-TrkB Signaling:
AKT1
→
Complex of TSC1-TSC2
(mim-inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
AKT1
—
TSC1
(physical association, affinity chromatography technology)
Roux et al., Proc Natl Acad Sci U S A 2004
-
IRef Biogrid Interaction:
AKT1
—
TSC1
(physical association, affinity chromatography technology)
Dan et al., J Biol Chem 2002*
-
IRef Hprd Interaction:
AKT1
—
TSC1
(in vivo)
Dan et al., J Biol Chem 2002*
-
MIPS Negatome - no physical interaction between proteins Interaction:
AKT1
—
TSC1
(Absence of interaction, coimmunoprecipitation)
Rosner et al., Mutat Res 2008
-
IRef Ophid Interaction:
AKT1
—
TSC1
(aggregation, confirmational text mining)
Dan et al., J Biol Chem 2002*
-
IRef Ophid Interaction:
AKT1
—
TSC1
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
-
STRING interaction:
AKT1
—
TSC1
(interaction, mapped from kegg_pathways)
-
STRING interaction:
AKT1
—
TSC1
(interaction, mapped from kegg_pathways)
-
STRING interaction:
TSC1
—
AKT1
(interaction, mapped from grid)
-
STRING interaction:
TSC1
—
AKT1
(interaction, mapped from grid)
Text-mined interactions from Literome
Potter et al., Nat Cell Biol 2002
:
Stimulating
Akt/PKB signalling in vivo markedly
increases cell growth/size, disrupts the Tsc1-Tsc2 complex and disturbs the distinct subcellular localization of
Tsc1 and Tsc2
Potter et al., Biochem Soc Trans 2003
:
We have shown that
Akt regulates the
Tsc1-Tsc2 complex by directly phosphorylating Tsc2
Dan et al., J Immunol 2008
:
mTOR is negatively controlled by the
tuberous sclerosis complex 1/2 (TSC1/2) , and activation of
Akt induces phosphorylation of TSC2, which blocks the repressive TSC1/2 activity
Pollizzi et al., Molecular cancer 2009
(Disease Models, Animal...) :
Loss of either
TSC1 or TSC2 in TSC hamartomas
leads to activation of mTORC1 and suppression of
AKT
Zhang et al., PloS one 2009
:
Loss of function of the
TSC1-TSC2 complex results in constitutive mTORC1 signaling and, through mTORC1 dependent feedback mechanisms and loss of mTORC2 activity,
leads to a concomitant block of
Akt signaling to its other downstream targets
Blancquaert et al., Mol Endocrinol 2010
:
Unlike insulin, TSH/cAMP did not activate
protein kinase B or
induce tuberous sclerosis complex 2 phosphorylation at T1462 and Y1571
Vadlakonda et al., Frontiers in oncology 2013
:
Akt phosphorylated at T308
inhibits TSC1/2 complex to activate mTORC1 ; mTORC2 is recognized as the kinase phosphorylating Akt at S473