background:
Akt, protein kinase B (PKB), is a serine/threonine kinase which is involved in many cellular signaling pathways and acts as a transducer of many functions initiated by growth factor receptors that activate phosphtidylinositol 3 kinase (PI 3 kinase). The major activity of Akt/PKB is to mediate cell survival. Akt/PKB is also believed to be a critical factor in the genesis of cancer as the tumor suppressor PTEN was found to antagonise PI3 kinase and Akt/PKB kinase activity. There are 3 known isoforms of this enzyme in mammalian cells (1/alpha, 2/beta and 3/gamma). IGF1 leads to the activation of AKT3, which may play a role in regulating cell survival. It is capable of phosphorylating several known proteins.
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.
Subunit:
Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation. Interacts with TRAF6.
Subcellular Location:
Cytoplasm. Nucleus. Cell membrane. Note=Nucleus after activation by integrin-linked protein kinase 1 (ILK1). Nuclear translocation is enhanced by interaction with TCL1A. Phosphorylation on Tyr-176 by TNK2 results in its localization to the cell membrane where it is targeted for further phosphorylations on Thr-308 and Ser-473 leading to its activation and the activated form translocates to the nucleus.
Tissue Specificity:
Widely expressed. Low levels found in liver with slightly higher levels present in thymus and testis.
Post-translational modifications:
Phosphorylation on Thr-305 and Ser-472 is required for full activity (By similarity).
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.
DISEASE:
Note=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 (MPPH) [MIM:603387]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Similarity:
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
Contains 1 AGSLCkinase SLCterminal domain.
Contains 1 PH domain.
Contains 1 protein kinase domain.
Database links:
Entrez Gene: 100137872 Cow
Entrez Gene: 10000 Human
Entrez Gene: 23797 Mouse
Entrez Gene: 29414 Rat
Omim: 611223 Human
SwissProt: Q9Y243 Human
SwissProt: Q9WUA6 Mouse
SwissProt: Q63484 Rat
Unigene: 498292 Human
Unigene: 235194 Mouse
Unigene: 10506 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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