| Description |
AKT1 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 (PMID:15526160, PMID:11882383, PMID:21620960, PMID:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PMID:15526160, PMID:11882383, PMID:21620960, PMID:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PMID:15526160, PMID:11882383, PMID:21620960, PMID:21432781). 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 (PMID:11994271). 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) (PMID:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PMID:11154276). 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 (PMID:12150915). 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 (PMID:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PMID:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PMID:10358075). 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) (PMID:9829964). 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 (PMID:9829964). 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 PI3P-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 (PI3K) 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) (PMID:12176338, PMID:12964941). AKT mediates the antiapoptotic effects of IGF-I . Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PMID:19934221). May be involved in the regulation of the placental development . Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PMID:17726016). Phosphorylates STK3/MST2 at 'Thr-117' and 'Thr-384' leading to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation (PMID:20086174, PMID:20231902). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PMID:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PMID:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PMID:10926925). Phosphorylates KAT6A at 'Thr-369' and this phosphorylation inhibits the interaction of KAT6A with PML and negatively regulates its acetylation activity towards p53/TP53 (PMID:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PMID:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PMID:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PMID:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PMID:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PMID:20682768). Phosphorylates PCK1 at 'Ser-90', reducing the binding affinity of PCK1 to oxaloacetate and changing PCK1 into an atypical protein kinase activity using GTP as donor (PMID:32322062). |
| Other names |
RAC-alpha serine/threonine-protein kinase, Protein kinase B, PKB, Protein kinase B alpha, PKB alpha, Proto-oncogene c-Akt, RAC-PK-alpha, PKB, RAC, AKT1, antibody |
