Summary

Name AKT2
Full Name RAC-beta serine/threonine-protein kinase
Synonyms Protein kinase Akt-2, Protein kinase B beta, PKB beta, RAC-PK-beta
Primary ID P31751
Links - -
Type protein
Relations 111
Pathways P38 Signaling and Myogenesis
Inhibitors GSK690693; MK-2206; CCT128930
Function AKT2 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT is responsible of the regulation of glucose uptake by mediating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport. AKT regulates also the storage of glucose in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', resulting in inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven. AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling and leading to both phosphorylation of 4E-BP1 and in activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), leading to binding of 14-3-3 proteins and cytoplasmic localization. In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated on equivalent sites. AKT has an important role in the regulation of NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). The phosphorylation of CREB1 induces the binding of accessory proteins that are necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis. Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate and its phosphorylation is implicated in the regulation cell proliferation and cell growth. AKT plays a role as key modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including correct neuron positioning, dendritic development and synapse formation. Signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors such as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. May be involved in the regulation of the placental development.; FUNCTION

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation BAD 0.28
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CREB1 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.14
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation ESR1 0.14
Publications: 1 Organism: Chlorocebus Aethiops
+ up-regulates img/direct-activation.png phosphorylation EP300 0.2
Publications: 2 Organism: Homo Sapiens
Tissue: Muscle
+ down-regulates img/direct_inhibition.png phosphorylation KHSRP 0.14
Publications: 1 Organism: Rattus Norvegicus
Pathways:P38 Signaling and Myogenesis
+ down-regulates img/direct_inhibition.png phosphorylation CASP9 0.2
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation HTRA2 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation FOXO3 0.2
Publications: 3
+ down-regulates activity img/direct_inhibition.png phosphorylation FOXO3 0.28
Publications: 3 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation FOXO 0.25
Publications: 8 Organism: Homo Sapiens, Mus Musculus
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation FOXO 0.25
Publications: 3
+ down-regulates activity img/direct_inhibition.png phosphorylation FOXO1 0.28
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation SH3RF1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation BMI1 0.14
Publications: 1
+ down-regulates img/direct_inhibition.png phosphorylation BRAF 0.14
Publications: 3 Organism: Homo Sapiens
+ img/unknown.png phosphorylation ACLY 0.28
Publications: 1 Organism: Rattus Norvegicus
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT2 0.2
Publications: 4 Organism: Mus Musculus, Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT2 0.28
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT2 0.4
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation AKT2 0.14
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation AKT2 0.42
Publications: 3 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle, Myotube
+ down-regulates activity img/direct_inhibition.png phosphorylation PTPN1 0.22
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png phosphorylation CTNNB1 0.28
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation PPARGC1A 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation, binding NOS3 0.14
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation HSPB1 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MAP3K5 0.28
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates img/direct-activation.png phosphorylation XIAP 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B 0.34
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation TSC2 0.45
Publications: 6 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation ANKRD2 0.28
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation STK3 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation CDKN1B 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation CHUK 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation POU5F1 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation AKT1S1 0.23
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation AKT2 0.14
Publications: 1 Organism: In Vitro
+ down-regulates activity img/direct_inhibition.png phosphorylation FOXO4 0.31
Publications: 3 Organism: Mus Musculus, Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation STK4 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation EZR 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding AKT2 0.38
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation GSK3B/Axin/APC 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation AKT1S1 0.23
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png dephosphorylation AKT2 0.4
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/indirect-activation.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ img/unknown.png dephosphorylation AKT2 0.34
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png GLI1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding AKT2 0.34
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding CDKN1A 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation CTNNB1 0.28
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation P300/PCAF 0.14
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle
Pathways:P38 Signaling and Myogenesis
+ up-regulates activity img/direct-activation.png phosphorylation mTORC1 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation IKK-complex 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png NFKB1 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png AKT2 0.22
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png MAPK14 0.14
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ down-regulates img/direct_inhibition.png phosphorylation GSK3A 0.22
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation TSC1/TSC2 0.14
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png dephosphorylation AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding AKT2 0.14
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/indirect-activation.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ up-regulates img/indirect-activation.png MTOR 0.14
Publications: 1 Organism: Homo Sapiens
Tissue: Muscle, Skeletal Muscle
+ up-regulates img/direct-activation.png binding AKT2 0.31
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding AKT2 0.31
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/indirect_inhibition.png AKT2 0.14
Publications: 1 Organism: Homo Sapiens
Pathways:P38 Signaling and Myogenesis
+ down-regulates activity img/direct_inhibition.png phosphorylation RAF1 0.14
Publications: 1 Organism: Homo Sapiens