AKT2

AKT2 Background

RAC-beta serine/threonine-protein kinase (AKT2) is an enzyme that in humans is encoded by the AKT2 gene ^[1], which is a putative oncogene. AKT2 regulates many processes, including metabolism, proliferation, cell survival, growth, and angiogenesis. All these processes are mediated through serine and/or threonine phosphorylation of a range of downstream substrates. AKT2 might serve as a more direct and specific kinase mediating Glucocorticoid resistance through FoxO3a/Bim signaling pathway. And AKT2 inhibition may be explored as a promising target for treating Glucocorticoids-resistant hematopoietic malignancies ^[2]. CDK9 acts as a proto-oncogene in cervical cancer and modulates cell proliferation and apoptosis through the AKT2/p53 pathway ^[3]. AKT2 increases the migration and invasion of ovarian cancer cells in vitro and promotes lung metastasis in nude mice in vivo through PKM2-mediated elevation of STAT3 expression and NF-kappaB activation ^[4]. Tang Y et al. provided evidence suggesting that AKT2 drives de novo lipogenesis in adipocytes by stimulating ChREBP beta transcriptional activity. The AKT2-ChREBP pathway in brown adipose tissue could optimize fuel storage and thermogenesis ^[5]. MiR-92a could inhibit the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) by regulating AKT2 expression ^[6].

[1] Cheng JQ, Godwin AK, et al. AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas [J]. Proc Natl Acad Sci U S A. November 1992, 89 (19): 9267-71.
[2] Xie M, Yang A, et al. Akt2 mediates glucocorticoid resistance in lymphoid malignancies through FoxO3a/Bim axis and serves as a direct target for resistance reversal [J]. Cell Death Dis. 2019 Jan 1;9(10):1013. doi: 10.1038/s41419-018-1043-6.
[3] Xu J, Xu S,et al. Cyclin-dependent kinase 9 promotes cervical cancer development via AKT2/p53 pathway [J]. IUBMB Life. 2019 Mar;71(3):347-356.
[4] Zheng B, Geng L, et al. AKT2 contributes to increase ovarian cancer cell migration and invasion through the AKT2-PKM2-STAT3/NF-kappaB axis [J]. Cell Signal. 2018 May;45:122-131.
[5] Sanchez-Gurmaches J, Tang Y, et al. Brown Fat AKT2 Is a Cold-Induced Kinase that Stimulates ChREBP-Mediated De Novo Lipogenesis to Optimize Fuel Storage and Thermogenesis [J]. Cell Metab. 2018 Jan 9;27(1):195-209.e6.
[6] Yu FY, Xie CQ, et al. MiR-92a inhibits fibroblast-like synoviocyte proliferation and migration in rheumatoid arthritis by targeting AKT2 [J]. J Biosci. 2018 Dec;43(5):911-919.