AKT3
The protein encoded by this gene is a member of the AKT, also called PKB, serine/threonine protein kinase family. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]
Full Name
AKT Serine/Threonine Kinase 3
Function
AKT3 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. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial for the viability of malignant glioma cells. AKT3 isoform may also be the key molecule in up-regulation and down-regulation of MMP13 via IL13. Required for the coordination of mitochondrial biogenesis with growth factor-induced increases in cellular energy demands. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis.
Biological Process
Brain morphogenesis Source: Ensembl
Homeostasis of number of cells within a tissue Source: Ensembl
Intracellular signal transduction Source: GO_Central
Mitochondrial genome maintenance Source: UniProtKB
Negative regulation of cellular senescence Source: BHF-UCL
Peptidyl-serine phosphorylation Source: GO_Central
Positive regulation of angiogenesis Source: Ensembl
Positive regulation of artery morphogenesis Source: Ensembl
Positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
Positive regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
Positive regulation of cell size Source: Ensembl
Positive regulation of endothelial cell proliferation Source: BHF-UCL
Positive regulation of TOR signaling Source: Ensembl
Positive regulation of vascular endothelial cell proliferation Source: BHF-UCL
Protein phosphorylation Source: ProtInc
Signal transduction Source: UniProtKB
Cellular Location
Cytoplasm; Nucleus; Membrane. Membrane-associated after cell stimulation leading to its translocation.
Involvement in disease
AKT3 is a key modulator of several tumors like melanoma, glioma and ovarian cancer. Active AKT3 increases progressively during melanoma tumor progression with highest levels present in advanced-stage metastatic melanomas. Promotes melanoma tumorigenesis by decreasing apoptosis. Plays a key role in the genesis of ovarian cancers through modulation of G2/M phase transition. With AKT2, plays a pivotal role in the biology of glioblastoma.
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (MPPH2): A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome.
PTM
Phosphorylation on Thr-305 and Ser-472 is required for full activity.
Ubiquitinated. When fully phosphorylated and translocated into the nucleus, undergoes 'Lys-48'-polyubiquitination catalyzed by TTC3, leading to its degradation by the proteasome.
O-GlcNAcylation at Thr-302 and Thr-309 inhibits activating phosphorylation at Thr-305 via disrupting the interaction between AKT and PDK1.