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mTOR kinase activity is required by the myocardium for basal level and insulin‐induced mTOR‐mediated signals
Author(s) -
Shen Weihua,
Chen Zhuang,
Penner Anne,
Shou Weinian,
Liechty Edward A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a818-c
Subject(s) - pi3k/akt/mtor pathway , rptor , phosphorylation , microbiology and biotechnology , kinase , protein kinase b , insulin , biology , cell growth , mtorc2 , protein kinase a , chemistry , signal transduction , endocrinology , mtorc1 , biochemistry
Using rapamycin, previous cell culture studies have suggested the role of mTOR in the regulation of cell proliferation and cell growth. The role of mTOR kinase activity in an intact animal remains poorly understood. The objective of this study is to investigate the role of mTOR kinase activity in animal development and growth and insulin‐induced signals using transgenic mouse as a model. The mTOR mutant proteins [mTOR kinase dead mutant (mTORkd) and constitutively active mutant (mTORca)] were overexpressed in the heart of mice. The results showed that overexpression of mTORkd (point mutation, D2338A) or mTORca (deletion of amino acids 2430–2450) by 3‐5fold did not lead to demonstrable morphologic phenotype in the mice. Nevertheless, it was found that mTORkd mice had reduced mTOR‐mediated 4EBP1/p70S6k phosphorylation, while overexpression of mTORca increased 4EBP1/p70S6k phosphorylation. Insulin was able to increase protein synthesis and 4EBP1/p70S6k phosphorylation in the heart of both mTORca and nontransgenic (NTg) littermate, but the insulin signal was largely inhibited in mTORkd mice. It is concluded that mTOR kinase activity is required by the myocardium for basal level and insulin‐induced mTOR‐mediated signals in vivo. Functional mTOR in vivo requires its association to other proteins. This work was supported by National Institutes of Health Grant and the Riley Children's Foundation.