Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin-responsive cells.
Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin-responsive cells.
复制标题
胰岛素反应细胞中雷帕霉素哺乳动物靶标的表达、酶活性和亚细胞定位。
DOI:
10.1006/bbrc.1997.7878
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发表时间:
1997
期刊:
影响因子:
--
通讯作者:
Shepherd,PR
中科院分区:
文献类型:
--
作者:
Withers,DJ;Ouwens,DM;Nave,BT;vanderZon,GC;Alarcon,CM;Cardenas,ME;Heitman,J;Maassen,JA;Shepherd,PR
The role of the mammalian target of rapamycin (mTOR) was investigated in insulin responsive cell lines. mTOR was expressed at high levels in insulin responsive cell types and in 3T3-L1 cells mTOR expression levels increased dramatically as cells differentiated from fibroblasts into insulin responsive adipocytes. mTOR localized to membrane fractions in all cells tested and in 3T3-L1 adipocytes mTOR was specifically localized to microsomal membranes. Protein kinase activity directed towards mTOR was tightly associated with mTOR immunoprecipitates and this kinase activity was inhibited by FKBP12-rapamycin indicating it was due to an autokinase activity present in mTOR. The mTOR autokinase and the protein kinase activity of the p110α isoform of PI 3-kinase shared several notable similarities; (a) both were maximally active in the presence of Mn2+but also showed significant activity in the presence of Mg2+(b) neither were inhibited by the presence of non-ionic detergent and (c) both were inhibited by wortmannin and LY294002, known inhibitors of the PI 3-kinase lipid kinase activity. These data taken together indicate the autokinase activity lay in the PI 3-kinase homology domain. In summary mTOR is a membrane anchored protein kinase that is active in conditions encountered in vivo and the fact it is highly expressed in insulin responsive cell types is consistent with a role in insulin signalling.
影响因子:
4.8
作者:
P. Chang;Y. Le Marchand;L. Cheatham;D. Moller
通讯作者:
D. Moller
DOI:
10.1113/jphysiol.1996.sp021594
发表时间:
1996
期刊:
The Journal of Physiology
影响因子:
--
作者:
S. Low;M. Rennie;P. Taylor
通讯作者:
P. Taylor