Akt1 iso2
an oncogenic AGC kinase that plays a critical role in regulating many processes including cell survival, metabolism, proliferation, growth and angiogenesis. Over 160 protein substrates are known including many that regulate transcription, metabolism, apoptosis, cell cycle, and growth. The activation of phosphatidylinositol 3-kinase alpha (PIK3CA) at the plasma membrane generates phosphatidylinositol 3,4,5-trisphosphate (PIP3), which binds to the PH domain of Akt, inducing its translocation to the plasma membrane. Dual phosphorylation is required for its activation. T308 is phosphorylated by PDK1 in the PI3 kinase pathway, and S473 is phosphorylated by mTOR in the mTORC2 pathway. The 'Lys-63'-linked ubiquitination of AKT1 by TRAF6 is important for its translocation to the plasma membrane, phosphorylation, and activation. When Akt is fully phosphorylated it translocates into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its proteosomal degradation. Hyperactive or overexpressed in a number of cancers including breast, prostate, lung, pancreatic, liver, ovarian and colorectal. Two alternatively-spliced human isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.1; Kinase, protein; Oncoprotein; Protein kinase, AGC; Protein kinase, Ser/Thr (non-receptor)
Molecular Function: 14-3-3 protein binding; ATP binding; calmodulin binding; enzyme binding; identical protein binding; kinase activity; nitric-oxide synthase regulator activity; phosphatidylinositol-3,4,5-trisphosphate binding; phosphatidylinositol-3,4-bisphosphate binding; potassium channel activator activity; protein binding; protein homodimerization activity; protein kinase activity; protein kinase binding; protein serine kinase activity; protein serine/threonine kinase activity; protein serine/threonine kinase inhibitor activity; protein serine/threonine/tyrosine kinase activity
Biological Process: activation-induced cell death of T cells; anoikis; apoptotic mitochondrial changes; behavioral response to pain; carbohydrate transport; cell differentiation; cell migration involved in sprouting angiogenesis; cell population proliferation; cellular response to cadmium ion; cellular response to decreased oxygen levels; cellular response to epidermal growth factor stimulus; cellular response to granulocyte macrophage colony-stimulating factor stimulus; cellular response to insulin stimulus; cellular response to nerve growth factor stimulus; 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; cytokine-mediated signaling pathway; epidermal growth factor receptor signaling pathway; establishment of protein localization to mitochondrion; excitatory postsynaptic potential; execution phase of apoptosis; fibroblast migration; G protein-coupled receptor signaling pathway; gene expression; glucose homeostasis; glucose metabolic process; glycogen biosynthetic process; I-kappaB kinase/NF-kappaB signaling; inflammatory response; insulin receptor signaling pathway; insulin-like growth factor 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; mammalian oogenesis stage; mammary gland epithelial cell differentiation; maternal placenta development; mitigation of host antiviral defense response; negative regulation of apoptotic process; negative regulation of autophagy; 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 innate immune response; 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 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 blood vessel endothelial cell migration; positive regulation of cell growth; positive regulation of cell population proliferation; positive regulation of cyclin-dependent protein serine/threonine kinase activity; positive regulation of DNA-binding transcription factor activity; positive regulation of DNA-templated transcription; positive regulation of endodeoxyribonuclease activity; positive regulation of endothelial cell migration; positive regulation of endothelial cell proliferation; 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 endoplasmic reticulum; positive regulation of protein localization to nucleus; positive regulation of protein localization to plasma membrane; positive regulation of protein metabolic process; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell proliferation; positive regulation of sodium ion transport; positive regulation of TORC1 signaling; positive regulation of transcription by RNA polymerase II; proteasome-mediated ubiquitin-dependent protein catabolic process; protein autophosphorylation; 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 postsynapse organization; regulation of signal transduction by p53 class mediator; regulation of translation; regulation of tRNA methylation; regulation of type B pancreatic cell development; response to fluid shear stress; response to food; response to growth factor; response to growth hormone; response to heat; response to insulin-like growth factor stimulus; response to oxidative stress; response to UV-A; signal transduction; sphingosine-1-phosphate receptor signaling pathway; striated muscle cell differentiation; T cell costimulation; TOR signaling
