Akt，亦被称为蛋白激酶B（PKB），是在如如葡萄糖代谢、凋亡、细胞增殖转录及细胞迁移等多种细胞过程中起到重要作用的一种丝氨酸/苏氨酸特异性蛋白激酶。
家族成员
Akt1通过抑制凋亡过程从而参与细胞存活途径。Akt1亦能诱导蛋白合成通路，故其在导致骨骼肌肥大及的一般组织生长的细胞通路中是一种重要信号蛋白。因其可以阻断凋亡并继而促进细胞存活，现已表明Akt1在多种肿瘤中起到主要作用。Akt（先亦被称为Akt1）首先是在转化逆转录病毒AKT8中被鉴定为癌基因的[3]。
Akt2在胰岛素信号通路中是一重要的信号分子。需要其来诱导葡萄糖转运。在敲除Akt1但具正常Akt2的小鼠中，血糖稳态不受干扰，但动物体型会较小，这与Akt1在生长中起得作用是一致的。相反，Akt2缺失但具有正常Akt1的的小鼠生长略缺陷且表现出糖尿病表型（胰岛素抵抗），这从另一方面印证了Akt2对胰岛素受体信号通路更具特异性的这一设想[4]。
Akt3似乎主要在脑中表达，但其作用仍未明晰。有报道显示Akt3缺失的小鼠脑部较小[5]。
参考文献
- ↑ 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]oxy}-1H-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.
深入阅读
- 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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