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| Role for Akt3/Protein kinase B gamma in attainment of normal brain size |
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| Author(s): Easton RM, Cho H, Roovers K, Shineman DW, Mizrahi M, Forman MS, Lee VMY, Szabolcs M, de Jong R, Oltersdorf T, Ludwig T, Efstratiadis A, Birnbaum MJ |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 25 Issue: 5 Pages: 1869-1878 Published: MAR 2005 |
| Times Cited: 126 References: 76 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Birnbaum, MJ (reprint author), Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Med, Clin Res Bldg 322,415 Curie Blvd, Philadelphia, PA 19104 USA |
Addresses:
1. Univ Penn, Sch Med, Ctr Neurodegenerat Dis Res, Dept Med, Philadelphia, PA 19104 USA
2. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
3. Univ Penn, Sch Med, Inst Aging, Philadelphia, PA 19104 USA
4. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
5. Dartmouth Coll Sch Med, Dept Genet, Hanover, NH USA
6. Columbia Univ, Dept Pathol, New York, NY 10027 USA
7. Columbia Univ, Dept Anat & Cell Biol, New York, NY 10027 USA
8. Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA
9. Columbia Univ, Inst Canc Genet, New York, NY 10027 USA
10. IDUN Pharmaceut Inc, San Diego, CA USA
11. Syrrx Inc, San Diego, CA USA |
| Publisher: AMER SOC MICROBIOLOGY, 1752 N ST NW, WASHINGTON, DC 20036-2904 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 898OI |
| ISSN: 0270-7306 |
| DOI: 10.1128/MCB.25.5.1869-1878.2005 |
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