Document Type

Article

Publication Date

3-2005

Publication Title

Molecular and Cellular Biology

Department

Geisel School of Medicine

Abstract

Studies of Drosophila 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.

DOI

10.1128/MCB.25.5.1869-1878.2005

Original Citation

Easton RM, Cho H, Roovers K, Shineman DW, Mizrahi M, Forman MS, Lee VM, Szabolcs M, de Jong R, Oltersdorf T, Ludwig T, Efstratiadis A, Birnbaum MJ. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol. 2005 Mar;25(5):1869-78. doi: 10.1128/MCB.25.5.1869-1878.2005. PMID: 15713641; PMCID: PMC549378.

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