Role for Akt3/Protein kinase Bγ in attainment of normal brain size
Role for Akt3/Protein kinase Bγ in attainment of normal brain size
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DOI：
10.1128/mcb.25.5.1869-1878.2005
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发表时间：
2005-03-01
影响因子：
5.3
通讯作者：
Birnbaum, MJ
中科院分区：
文献类型：
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作者：
Easton, RM;Cho, H;Birnbaum, MJ
果蝇属和哺乳动物的研究已经揭示了通过磷脂酰肌醇3-激酶和丝氨酸/苏氨酸激酶Akt/蛋白激酶B的胰岛素信号传导对于调节细胞、器官和生物体生长的重要性。在哺乳动物中，三种高度保守的蛋白质，Akt 1，Akt 2和Akt 3，组成Akt家族，其中前两种分别是正常生长和代谢所需的。在这里，我们讨论Akt 3的功能。与Akt 1一样，Akt 3不是维持正常碳水化合物代谢所必需的，但对于获得正常器官大小至关重要。然而，与Akt 1（-/-）小鼠相比，Akt 3（-/-）小鼠显示出所有器官大小成比例的减少，大脑大小选择性减少20%。此外，尽管Akt 1和Akt 3缺陷的大脑在大小上减小到大致相同的程度，但Akt 1的缺乏导致细胞数量减少，而Akt 3的缺乏导致更小和更少的细胞。最后，哺乳动物雷帕霉素靶信号在Akt 3（-/-）小鼠脑中减弱，但在Akt 1（-/-）小鼠脑中未减弱，表明该途径的差异调节有助于细胞生长的亚型特异性调节。
Studies of Drosaphila and mammals have revealed the importance of insulin signaling through phosphatidylinositol 3-kinase and the serine/threonine kinase Akt/protein kinase B for the regulation of cell, organ, and organismal growth. In mammals, three highly conserved proteins, Akt1, Akt2, and Akt3, comprise the Akt family, of which the first two are required for normal growth and metabolism, respectively. Here we address the function of Akt3. Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. However, in contrast to Akt1(-/-) mice, which display a proportional decrease in the sizes of all organs, Akt3(-/-) mice present a selective 20% decrease in brain size. Moreover, although Akt1- and Akt3-deficient brains are reduced in size to approximately the same degree, the absence of Akt1 leads to a reduction in cell number, whereas the lack of Akt3 results in smaller and fewer cells. Finally, mammalian target of rapamycin signaling is attenuated in the brains of Akt3(-/-) but not Akt1(-/-) mice, suggesting that differential regulation of this pathway contributes to an isoform-specific regulation of cell growth.