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AKT1 — MAPKAP1
Pathways - manually collected, often from reviews:
-
NCI Pathway Database CXCR3-mediated signaling events:
mTORC2 complex (MTOR-RICTOR-MLST8-MAPKAP1)
→
AKT1 (AKT1)
(modification, activates)
Bonacchi et al., J Biol Chem 2001, Smit et al., Blood 2003
Evidence: assay
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
mTORC2 complex (MTOR-RICTOR-MLST8-MAPKAP1)
→
AKT1 (AKT1)
(modification, activates)
Sarbassov et al., Science 2005, Frias et al., Curr Biol 2006, Jacinto et al., Cell 2006
Evidence: mutant phenotype, assay, physical interaction, other species
-
NCI Pathway Database CXCR4-mediated signaling events:
mTORC2 complex (MTOR-RICTOR-MLST8-MAPKAP1)
→
AKT1 (AKT1)
(modification, activates)
Sotsios et al., J Immunol 1999, Curnock et al., J Immunol 2003, Chen et al., Mol Biol Cell 2008
Evidence: assay
-
NCI Pathway Database ErbB1 downstream signaling:
mTORC2 complex (MTOR-RICTOR-MLST8-MAPKAP1)
→
AKT1 (AKT1)
(modification, activates)
Sarbassov et al., Science 2005, Cao et al., Science signaling 2009
Evidence: genetic interaction
-
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
-
Reactome Reaction:
AKT1
→
MAPKAP1
(reaction)
Scheid et al., Mol Cell Biol 2002*, Sarbassov et al., Science 2005, Carpten et al., Nature 2007*, Landgraf et al., Biochemistry 2008*
-
WikiPathways Angiopoietin Like Protein 8 Regulatory Pathway:
AKT1/AKT2
→
Complex of MTOR-MAPKAP1-RICTOR-MLST8
(activation)
-
WikiPathways Target Of Rapamycin (TOR) Signaling:
Complex of MLST8-MTOR-MAPKAP1-RICTOR
→
AKT1
(activation)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Woo et al., J Biol Chem 2007
(Breast Neoplasms...) :
Despite no significant effect of PRR5 on
mTORC2 mediated
Akt phosphorylation, PRR5 silencing inhibits Akt and S6K1 phosphorylation and reduces cell proliferation rates, a result consistent with PRR5 roles in cell growth and tumorigenesis
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
Julien et al., Mol Cell Biol 2010
:
While mTOR complex 1 (mTORC1) regulates mRNA translation and ribosome biogenesis,
mTORC2 plays an important role in the phosphorylation and subsequent activation of
Akt
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 ... 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
Murata et al., J Biol Chem 2011
(Neuroblastoma...) :
A new cytosolic pathway from a Parkinson disease associated kinase, BRPK/PINK1 :
activation of
AKT via
mTORC2
Harston et al., Am J Physiol Heart Circ Physiol 2011
(Hypertrophy) :
Another molecular keystone involved in the hypertrophic growth process is the mammalian target of rapamycin (mTOR), which forms two distinct functional complexes : mTORC1 that activates p70S6 kinase-1 to enhance protein synthesis and
mTORC2 that
activates Akt to promote cell survival
Pearce et al., Biochem J 2011
:
Both complexes phosphorylate the hydrophobic motifs of AGC kinase family members : mTORC1 phosphorylates S6K ( S6 kinase ), whereas
mTORC2 regulates phosphorylation of
Akt , PKCa ( protein kinase Ca ) and SGK1 ( serum- and glucocorticoid induced protein kinase 1 )
Gupta et al., Blood 2012
(Lymphoma) :
Dual
mTORC1/mTORC2 inhibition
diminishes Akt activation and induces Puma dependent apoptosis in lymphoid malignancies
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
Hussain et al., Mol Cell Biol 2013
:
Raptor bound mTOR ( mTORC1 ) governs cap dependent mRNA translation, whereas mTOR, rictor, and
mSin1 ( mTORC2 )
activate the survival and proliferative kinase
Akt
Yao et al., Science signaling 2013
:
The mammalian target of rapamycin complex 2 ( mTORC2 ) facilitated the phosphorylation of BSTA and its association with Akt1, and the
BSTA-Akt1 interaction
promoted the association of
mTORC2 with Akt1 and phosphorylation of Akt1 at Ser473 in response to growth factor stimulation
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