KinaseMD - AKT1

AKT1 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 (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed:21432781). Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported (PubMed:15526160, PubMed:11882383, PubMed:21620960, PubMed: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 (By similarity). Phosphorylation of PTPN1 at 'Ser-50' negatively modulates its phosphatase activity preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling (By similarity). Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, which is required for insulin-stimulated glucose transport (PubMed: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 (By similarity). Phosphorylation of GSK3 isoforms by AKT is also thought to be one mechanism by which cell proliferation is driven (By similarity). AKT regulates also cell survival via the phosphorylation of MAP3K5 (apoptosis signal-related kinase) (PubMed:11154276). Phosphorylation of 'Ser-83' decreases MAP3K5 kinase activity stimulated by oxidative stress and thereby prevents apoptosis (PubMed: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 (PubMed: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 (PubMed:10358075). In particular, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256' and 'Ser-319' (PubMed:10358075). FOXO3 and FOXO4 are phosphorylated on equivalent sites (PubMed: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) (PubMed: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 (PubMed:9829964). AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), thereby potentially regulating ACLY activity and fatty acid synthesis (By similarity). Activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis (By similarity). Phosphorylates PIKFYVE on 'Ser-318', which results in increased PI3P-5 activity (By similarity). 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 (By similarity). 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) (PubMed:12176338, PubMed:12964941). AKT mediates the antiapoptotic effects of IGF-I (By similarity). Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly (PubMed:19934221). May be involved in the regulation of the placental development (By similarity). Phosphorylates STK4/MST1 at 'Thr-120' and 'Thr-387' leading to inhibition of its: kinase activity, nuclear translocation, autophosphorylation and ability to phosphorylate FOXO3 (PubMed: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 (PubMed:20086174, PubMed:20231902). Phosphorylates SRPK2 and enhances its kinase activity towards SRSF2 and ACIN1 and promotes its nuclear translocation (PubMed:19592491). Phosphorylates RAF1 at 'Ser-259' and negatively regulates its activity (PubMed:10576742). Phosphorylation of BAD stimulates its pro-apoptotic activity (PubMed: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 (PubMed:23431171). Phosphorylates palladin (PALLD), modulating cytoskeletal organization and cell motility (PubMed:20471940). Phosphorylates prohibitin (PHB), playing an important role in cell metabolism and proliferation (PubMed:18507042). Phosphorylates CDKN1A, for which phosphorylation at 'Thr-145' induces its release from CDK2 and cytoplasmic relocalization (PubMed:16982699). These recent findings indicate that the AKT1 isoform has a more specific role in cell motility and proliferation (PubMed:16139227). Phosphorylates CLK2 thereby controlling cell survival to ionizing radiation (PubMed:20682768). View more >>

GO - Biological processes (BP): activation-induced cell death of T cells, activation of protein kinase B activity, aging, anoikis, apoptotic mitochondrial changes, carbohydrate transport, cell differentiation, cell migration involved in sprouting angiogenesis, cell population proliferation, cell projection organization, cellular response to cadmium ion, cellular response to DNA damage stimulus, cellular response to epidermal growth factor stimulus, cellular response to granulocyte macrophage colony-stimulating factor stimulus, cellular response to hypoxia, cellular response to insulin stimulus, cellular response to mechanical stimulus, cellular response to nerve growth factor stimulus, cellular response to organic cyclic compound, cellular response to oxidised low-density lipoprotein particle stimulus, cellular response to prostaglandin E stimulus, cellular response to reactive oxygen species, cellular response to tumor necrosis factor, cellular response to vascular endothelial growth factor stimulus, cofactor metabolic process, cytokine-mediated signaling pathway, endocrine pancreas development, epidermal growth factor receptor signaling pathway, establishment of protein localization to mitochondrion, excitatory postsynaptic potential, execution phase of apoptosis, germ cell development, glucose homeostasis, glucose metabolic process, glycogen biosynthetic process, glycogen cell differentiation involved in embryonic placenta development, G protein-coupled receptor signaling pathway, hyaluronan metabolic process, I-kappaB kinase/NF-kappaB signaling, inflammatory response, insulin-like growth factor receptor signaling pathway, insulin receptor signaling pathway, interleukin-18-mediated signaling pathway, intracellular signal transduction, labyrinthine layer blood vessel development, lipopolysaccharide-mediated signaling pathway, maintenance of protein location in mitochondrion, mammary gland epithelial cell differentiation, maternal placenta development, negative regulation of apoptotic process, negative regulation of autophagy, negative regulation of cell size, negative regulation of cysteine-type endopeptidase activity involved in apoptotic process, negative regulation of endopeptidase activity, negative regulation of extrinsic apoptotic signaling pathway in absence of ligand, negative regulation of fatty acid beta-oxidation, negative regulation of gene expression, negative regulation of JNK cascade, negative regulation of leukocyte cell-cell adhesion, negative regulation of long-chain fatty acid import across plasma membrane, negative regulation of lymphocyte migration, negative regulation of macroautophagy, negative regulation of neuron death, negative regulation of Notch signaling pathway, negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, negative regulation of protein binding, negative regulation of protein kinase activity, negative regulation of protein kinase activity by protein phosphorylation, negative regulation of protein kinase B signaling, negative regulation of protein serine/threonine kinase activity, negative regulation of protein ubiquitination, negative regulation of proteolysis, negative regulation of release of cytochrome c from mitochondria, NIK/NF-kappaB signaling, nitric oxide biosynthetic process, osteoblast differentiation, peptidyl-serine phosphorylation, peptidyl-threonine phosphorylation, peripheral nervous system myelin maintenance, phosphatidylinositol 3-kinase signaling, phosphorylation, positive regulation of apoptotic process, positive regulation of blood vessel endothelial cell migration, positive regulation of cell growth, positive regulation of cell population proliferation, positive regulation of cellular protein metabolic process, positive regulation of cyclin-dependent protein serine/threonine kinase activity, positive regulation of DNA-binding transcription factor activity, positive regulation of endodeoxyribonuclease activity, positive regulation of endothelial cell proliferation, positive regulation of epidermal growth factor receptor signaling pathway, positive regulation of fat cell differentiation, positive regulation of fibroblast migration, positive regulation of G1/S transition of mitotic cell cycle, positive regulation of gene expression, positive regulation of glucose import, positive regulation of glucose metabolic process, positive regulation of glycogen biosynthetic process, positive regulation of I-kappaB phosphorylation, positive regulation of lipid biosynthetic process, positive regulation of mitochondrial membrane potential, positive regulation of nitric oxide biosynthetic process, positive regulation of nitric-oxide synthase activity, positive regulation of organ growth, positive regulation of peptidyl-serine phosphorylation, positive regulation of proteasomal ubiquitin-dependent protein catabolic process, positive regulation of protein localization to cell surface, positive regulation of protein localization to nucleus, positive regulation of protein localization to plasma membrane, positive regulation of protein phosphorylation, positive regulation of smooth muscle cell proliferation, positive regulation of sodium ion transport, positive regulation of transcription, DNA-templated, positive regulation of transcription by RNA polymerase II, positive regulation of vasoconstriction, protein autophosphorylation, protein catabolic process, protein import into nucleus, protein kinase B signaling, protein phosphorylation, protein ubiquitination, regulation of apoptotic process, regulation of cell migration, regulation of glycogen biosynthetic process, regulation of mRNA stability, regulation of myelination, regulation of neuron projection development, regulation of nitric-oxide synthase activity, regulation of signal transduction by p53 class mediator, regulation of translation, response to fluid shear stress, response to food, response to growth hormone, response to heat, response to insulin-like growth factor stimulus, response to oxidative stress, response to UV-A, signal transduction, spinal cord development, striated muscle cell differentiation, T cell costimulation, TOR signaling, translation View more >>

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KinaseMD: Kinase mutations and drug responses

AKT1

Entrez ID: 207

Full name: AKT serine/threonine kinase 1

External links: HGNC UniprotKB Ensembl RefSeq COSMIC

Family: AGC: Akt

Chromosomal location: 14q32.33

Substructure location: Gatekeeper: 227 A-loop: 291...314 G-loop: 156...162 αC-helix: 183...188

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Kaplan plot for AKT1 in