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AKT1 — GSK3A

Pathways - manually collected, often from reviews:

• OpenBEL Selventa BEL large corpus: GSK3A → AKT1 (directlyDecreases, AKT1 Activity, GSK3A Activity) Fang et al., Proc Natl Acad Sci U S A 2000*
  Evidence: GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidylinositol 3-kinase.
• OpenBEL Selventa BEL large corpus: GSK3A → AKT1 (increases, AKT1 Activity, GSK3A Activity) Laine et al., J Biol Chem 2002*
  Evidence: Modified assertion
• OpenBEL Selventa BEL large corpus: GSK3A → AKT1 (directlyIncreases, GSK3A Activity) Fang et al., Proc Natl Acad Sci U S A 2000*
  Evidence: GSK-3 activity is inhibited through phosphorylation of serine 21 in GSK-3 alpha and serine 9 in GSK-3 beta. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidylinositol 3-kinase.
• OpenBEL Selventa BEL large corpus: GSK3A → AKT1 (increases, GSK3A Activity) Laine et al., J Biol Chem 2002*
  Evidence: Modified assertion
• BioCarta phosphoinositides and their downstream targets: AKT (AKT1) → GSK3-alpha (GSK3A) (modification, activates)
• KEGG Chemokine signaling pathway: AKT1/AKT2/AKT3 → GSK3A/GSK3B (protein-protein, inhibition)
• NCI Pathway Database Class I PI3K signaling events mediated by Akt: GSK3 (GSK3B/GSK3A) → AKT1 (AKT1) (modification, collaborate) Cross et al., Nature 1995
  Evidence: mutant phenotype, assay
• Reactome Reaction: AKT1 → GSK3A (reaction) Haq et al., Proc Natl Acad Sci U S A 2003*, Malanga et al., Cell cycle (Georgetown, Tex.) 2008*, Ueki et al., J Biol Chem 1998*
• WikiPathways Angiopoietin Like Protein 8 Regulatory Pathway: AKT1/AKT2 → GSK3A/GSK3B (inhibition)
• WikiPathways Regulation of Apoptosis by Parathyroid Hormone-related Protein: AKT1 → GSK3B/GSK3A (mim-inhibition)
• WikiPathways Sterol Regulatory Element-Binding Proteins (SREBP) signalling: AKT1 → GSK3A (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 — GSK3A (direct interaction, enzymatic study) Nakamura et al., J Immunol 2001*
• IRef Biogrid Interaction: AKT1 — GSK3A (direct interaction, enzymatic study) Ma et al., Mol Endocrinol 2007*
• IRef Biogrid Interaction: AKT1 — GSK3A (direct interaction, enzymatic study) Li et al., Mol Cell Biol 2003*
• IRef Biogrid Interaction: AKT1 — GSK3A (direct interaction, enzymatic study) Sundaresan et al., Science signaling 2011*
• IRef Biogrid Interaction: AKT1 — GSK3A (direct interaction, enzymatic study) Dragoi et al., EMBO J 2005*
• IRef Biogrid Interaction: AKT1 — GSK3A (direct interaction, enzymatic study) Drendall et al., Protein Expr Purif 2010*
• IRef Hprd Interaction: AKT1 — GSK3A (in vivo) Fang et al., Proc Natl Acad Sci U S A 2000*, Fang et al., Mol Cell Biol 2002*, Cross et al., Nature 1995
• IRef Hprd Interaction: AKT1 — GSK3A (in vitro) Fang et al., Proc Natl Acad Sci U S A 2000*, Fang et al., Mol Cell Biol 2002*, Cross et al., Nature 1995
• IRef Ophid Interaction: AKT1 — GSK3A (aggregation, interologs mapping) Brown et al., Bioinformatics 2005
• STRING interaction: AKT1 — GSK3A (interaction, mapped from kegg_pathways)
• STRING interaction: GSK3A — AKT1 (interaction, mapped from kegg_pathways)

Text-mined interactions from Literome

Shaw et al., FEBS Lett 1999 (MAP Kinase Signaling System) : Here, we show that protein kinase B (PKB) plays a key role in mediating EGF induced inhibition of GSK3alpha and that the classical MAP kinase ( MAPK ) cascade has two functions in this process ... Secondly, it shortens the duration of PKB activation and GSK3alpha inhibition ... In contrast, PKB alone mediates the IGF1 induced inhibition of GSK3alpha , while the MAPK cascade mediates the inhibition of GSK3alpha by PMA
Chen et al., Cancer Res 2001 (Fibrosarcoma) : Activation of Akt by hypoxia resulted in the phosphorylation of GSK-3alpha and GSK-3beta at Ser-9 and Ser-21, two well documented Akt phosphorylation sites, respectively, that are inactivating modifications of each GSK-3 isoform
Wrede et al., J Biol Chem 2002 (Necrosis) : Further analysis of pro-apoptotic downstream targets of PKB, implicated a role for PKB mediated phosphorylation inhibition of glycogen synthase kinase-3alpha/beta and the forkhead transcription factor, FoxO1, in protection of FFA induced beta-cell apoptosis
Ho et al., FASEB J 2004 (Alzheimer Disease...) : This latter finding is of particular interest given the known inhibitory role of AKT/PKB on glycogen synthase kinase (GSK)-3alpha activity, which has previously been shown to promote Abeta peptide generation
Beaulieu et al., Proc Natl Acad Sci U S A 2004 : In the mouse striatum, increased DA neurotransmission arising either from administration of amphetamine or from the lack of the DA transporter results in inactivation of Akt and concomitant activation of GSK-3alpha and GSK-3beta
Sale et al., Biochemistry 2006 : Triple antisense knock down of PKB alpha, beta, and gamma so that total PKB was < 6 % blocked insulin stimulated phosphorylation of endogenous GSK-3alpha and GSK-3beta isoforms by 67 % and 45 %, respectively, showing that GSK-3alpha and GSK-3beta are controlled by endogenous PKB
Højlund et al., Diabetologia 2006 : Insulin increased Akt phosphorylation at Ser473 and Thr308, inhibited glycogen synthase kinase-3alpha activity, reduced phosphorylation of glycogen synthase at sites 3a+3b, and increased glycogen synthase activity in Arg1174Gln carriers ( all p < 0.05 )
Ciaraldi et al., Endocrinology 2007 (Insulin Resistance) : However, GSK3alpha overexpression impaired insulin action on pS473-Akt
Li et al., Journal of molecular signaling 2009 : Phosphorylation of GSK3a/b ( glycogen synthase kinase 3 ), the downstream target of AKT/PKB, was inhibited by the AKT/PKB inhibitor
Blalock et al., J Cell Physiol 2009 (Leukemia) : PKR inhibition augmented levels of p-S473 AKT and p-S21/9 GSK-3alpha/beta in the presence of the PI3K inhibitor, LY294002, but was unable to augment GSK-3alpha or beta phosphorylation in the presence of the AKT inhibitor, A443654