Role for Akt3/protein kinase Bgamma in attainment of normal brain size.
Publication/Presentation Date
3-1-2005
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.
Volume
25
Issue
5
First Page
1869
Last Page
1878
ISSN
0270-7306
Published In/Presented At
Easton, R. M., Cho, H., Roovers, K., Shineman, D. W., Mizrahi, M., Forman, M. S., Lee, V. M., Szabolcs, M., de Jong, R., Oltersdorf, T., Ludwig, T., Efstratiadis, A., & Birnbaum, M. J. (2005). Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Molecular and cellular biology, 25(5), 1869–1878. https://doi.org/10.1128/MCB.25.5.1869-1878.2005
Disciplines
Medicine and Health Sciences
PubMedID
15713641
Department(s)
Department of Medicine
Document Type
Article