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J. Biol. Chem., Vol. 276, Issue 42, 38349-38352, October 19, 2001
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Is Required for Normal Growth but Dispensable for
Maintenance of Glucose Homeostasis in Mice*
§,
,,, and**
From the The serine-threonine kinase Akt, also
known as protein kinase B (PKB), is an important effector for
phosphatidylinositol 3-kinase signaling initiated by numerous
growth factors and hormones. Akt2/PKB Department of Biology, University of
Pennsylvania and the ¶ Department of Cell and Developmental
Biology, ** Department of Medicine, and Howard Hughes
Medical Institute, University of Pennsylvania School of Medicine,
Philadelphia, Pennsylvania 19104
, one of three known mammalian
isoforms of Akt/PKB, has been demonstrated recently to be required for
at least some of the metabolic actions of insulin (Cho, H., Mu,
J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw,
E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., and Birnbaum, M. J. (2001) Science
292, 1728-1731). Here we show that mice deficient in another closely
related isoform of the kinase, Akt1/PKB
, display a conspicuous
impairment in organismal growth. Akt1
/ mice
demonstrated defects in both fetal and postnatal growth, and these
persisted into adulthood. However, in striking contrast to Akt2/PKB
null mice, Akt1/PKB-deficient mice are normal with regard to glucose
tolerance and insulin-stimulated disposal of blood glucose. Thus, the
characterization of the Akt1 knockout mice and its
comparison to the previously reported Akt2 deficiency phenotype reveals the non-redundant functions of Akt1 and
Akt2 genes with respect to organismal growth and
insulin-regulated glucose metabolism.
To whom correspondence should be addressed. Tel.: 215-898-5001;
Fax: 215-573-9138; E-mail: birnbaum@mail.med.upenn.edu.
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