Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size

Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size Rachael M. Easton 1 , Han Cho 1 , 2 , Kristin Roovers 1 , Diana W. Shineman 3 , Moshe Mizrahi 4 , Mark S. Forman 3 , Virginia M.-Y. Lee 3 , Matthias Szabolcs 5 , Ron de Jong 6 , 7 , Tilman Oltersdorf 6 , Thomas Ludwig 8 , 9 , Argiris Efstratiadis 9 , 10 and Morris J. Birnbaum 1 , 4 , * 1 Department of Medicine, Center for Neurodegenerative Disease Research 3 Department of Pathology and Laboratory Medicine and Institute on Aging 4 Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 5 Departments of Pathology 8 Anatomy and Cell Biology 10 Genetics and Development 9 Institute for Cancer Genetics, Columbia University, New York, New York 6 IDUN Pharmaceuticals, Inc. 7 Syrrx, Inc., San Diego, California 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size

Molecular and Cellular Biology , Volume 25 (5): 1869 – Mar 1, 2005

Abstract

Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size Rachael M. Easton 1 , Han Cho 1 , 2 , Kristin Roovers 1 , Diana W. Shineman 3 , Moshe Mizrahi 4 , Mark S. Forman 3 , Virginia M.-Y. Lee 3 , Matthias Szabolcs 5 , Ron de Jong 6 , 7 , Tilman Oltersdorf 6 , Thomas Ludwig 8 , 9 , Argiris Efstratiadis 9 , 10 and Morris J. Birnbaum 1 , 4 , * 1 Department of Medicine, Center for Neurodegenerative Disease Research 3 Department of Pathology and Laboratory Medicine and Institute on Aging 4 Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 5 Departments of Pathology 8 Anatomy and Cell Biology 10 Genetics and Development 9 Institute for Cancer Genetics, Columbia University, New York, New York 6 IDUN Pharmaceuticals, Inc. 7 Syrrx, Inc., San Diego, California 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.

Loading next page...
 
/lp/american-society-for-microbiology/role-for-akt3-protein-kinase-b-in-attainment-of-normal-brain-size-sOUiXD3on8

References (80)

Publisher
American Society For Microbiology
Copyright
Copyright © 2005 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.25.5.1869-1878.2005
pmid
15713641
Publisher site
See Article on Publisher Site

Abstract

Role for Akt3/Protein Kinase Bγ in Attainment of Normal Brain Size Rachael M. Easton 1 , Han Cho 1 , 2 , Kristin Roovers 1 , Diana W. Shineman 3 , Moshe Mizrahi 4 , Mark S. Forman 3 , Virginia M.-Y. Lee 3 , Matthias Szabolcs 5 , Ron de Jong 6 , 7 , Tilman Oltersdorf 6 , Thomas Ludwig 8 , 9 , Argiris Efstratiadis 9 , 10 and Morris J. Birnbaum 1 , 4 , * 1 Department of Medicine, Center for Neurodegenerative Disease Research 3 Department of Pathology and Laboratory Medicine and Institute on Aging 4 Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 2 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 5 Departments of Pathology 8 Anatomy and Cell Biology 10 Genetics and Development 9 Institute for Cancer Genetics, Columbia University, New York, New York 6 IDUN Pharmaceuticals, Inc. 7 Syrrx, Inc., San Diego, California 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.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Mar 1, 2005

There are no references for this article.