Akt，亦被稱為蛋白激酶B（PKB），是在如如葡萄糖代謝、凋亡、細胞增殖轉錄及細胞遷移等多種細胞過程中起到重要作用的一種絲氨酸/蘇氨酸特異性蛋白激酶。
家族成員
Akt1通過抑制凋亡過程從而參與細胞存活途徑。Akt1亦能誘導蛋白合成通路，故其在導致骨骼肌肥大及的一般組織生長的細胞通路中是一種重要信號蛋白。因其可以阻斷凋亡並繼而促進細胞存活，現已表明Akt1在多種腫瘤中起到主要作用。Akt（先亦被稱為Akt1）首先是在轉化逆轉錄病毒AKT8中被鑒定為癌基因的[3]。
Akt2在胰島素信號通路中是一重要的信號分子。需要其來誘導葡萄糖轉運。在敲除Akt1但具正常Akt2的小鼠中，血糖穩態不受干擾，但動物體型會較小，這與Akt1在生長中起得作用是一致的。相反，Akt2缺失但具有正常Akt1的的小鼠生長略缺陷且表現出糖尿病表型（胰島素抵抗），這從另一方面印證了Akt2對胰島素受體信號通路更具特異性的這一設想[4]。
Akt3似乎主要在腦中表達，但其作用仍未明晰。有報導顯示Akt3缺失的小鼠腦部較小[5]。
參考文獻
- ↑ 1.0 1.1 PDB 3MV5; Freeman-Cook KD, Autry C, Borzillo G, Gordon D, Barbacci-Tobin E, Bernardo V, Briere D, Clark T, Corbett M, Jakubczak J, Kakar S, Knauth E, Lippa B, Luzzio MJ, Mansour M, Martinelli G, Marx M, Nelson K, Pandit J, Rajamohan F, Robinson S, Subramanyam C, Wei L, Wythes M, Morris J. Design of selective, ATP-competitive inhibitors of Akt. J. Med. Chem.. June 2010, 53 (12): 4615–22. doi:10.1021/jm1003842. PMID 20481595.
- ↑ PDB 3D0E; Heerding DA, Rhodes N, Leber JD, Clark TJ, Keenan RM, Lafrance LV, Li M, Safonov IG, Takata DT, Venslavsky JW, Yamashita DS, Choudhry AE, Copeland RA, Lai Z, Schaber MD, Tummino PJ, Strum SL, Wood ER, Duckett DR, Eberwein D, Knick VB, Lansing TJ, McConnell RT, Zhang S, Minthorn EA, Concha NO, Warren GL, Kumar R. Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7[(3S)-3-piperidinylmethyl]oxy1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J. Med. Chem.. September 2008, 51 (18): 5663–79. doi:10.1021/jm8004527. PMID 18800763.
- ↑ Staal SP, Hartley JW, Rowe WP. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC431413/ Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma]. Proc. Natl. Acad. Sci. U.S.A.. July 1977, 74 (7): 3065–7. doi:10.1073/pnas.74.7.3065. PMID 197531. PMC 431413.
- ↑ Garofalo RS, Orena SJ, Rafidi K, Torchia AJ, Stock JL, Hildebrandt AL, Coskran T, Black SC, Brees DJ, Wicks JR, McNeish JD, Coleman KG. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC164287/ Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta]. J. Clin. Invest.. July 2003, 112 (2): 197–208. doi:10.1172/JCI16885. PMID 12843127. PMC 164287.
- ↑ Yang ZZ, Tschopp O, Baudry A, Dümmler B, Hynx D, Hemmings BA. Physiological functions of protein kinase B/Akt. Biochem. Soc. Trans.. April 2004, 32 (Pt 2): 350–4. doi:10.1042/BST0320350. PMID 15046607.
深入閱讀
- Los M, Maddika S, Erb B, Schulze-Osthoff K. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC2954189/ Switching Akt: from survival signaling to deadly response]. BioEssays. May 2009, 31 (5): 492–5. doi:10.1002/bies.200900005. PMID 19319914. PMC 2954189.
- Quaresma AJ, Sievert R, Nickerson JA. [http//www.ncbi.nlm.nih.gov/pmc/articles/PMC3623641/ Regulation of mRNA export by the PI3 kinase/AKT signal transduction pathway.]. Mol. Biol. Cell.. 2013, April (8): 1208-21. doi:10.1091/mbc.E12-06-0450. PMID 23427269. PMC 3623641.
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