Akt, also called RAC (related to protein kinase A and C) or protein kinase B (PKB), is a 57 kD serine/threonine kinases family which is the central mediator of the PI3K pathway with numerous downstream molecules that influence important cellular processes. Akt could be activated by insulin and various growth factors (VGF) in a series of wortmannin-sensitive PI3K cascades [1,2]. Responding to up-stream signaling pathways, Akt is phosphorylated at Thr308 by PDK1and at Ser473 by PDK2 [4,5]. After Akt activation, it could phosphorylate a variety of downstream molecules related to the regulation of cell proliferation including glycogen synthase kinase-3 (GSK-3) [6,7], Bad, PAK1, CREB and p27 and suppress cell apoptosis . Akt directly phosphorylates mTOR in mTORC1, a rapamycin-sensitive complex . Akt could also deactivate tuberin (TSC2), an inhibitor of mTORC1 [11,12]. There are three Akt genes in mammalian genomes, which encode Akt1(PKBα), Akt2(PKBβ) and Akt3(PKBγ), respectively . All Akt isoforms have similar structural homology. Akt2 has 81% homology with Akt1, and Akt3 83% . All three Akt subtypes are widely expressed in mammalian cells, however Akt 1 is most expressed in brain, heart, and lung, while Akt2 is predominantly located in skeletal muscle and embryonic brown fat and Akt3 is mainly expressed in brain, kidney, and embryonic heart [15-18]. Evidences suggested that Akt is associated with the survival, proliferation, migration and infiltration of many kinds of cancer cells. Perifosine (also KRX-0401), an Akt and PI3K inhibitor, has orphan drug status for the treatment of multiple myeloma and neuroblastoma in the US .
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