Journal
CANCER RESEARCH
Volume 69, Issue 5, Pages 1821-1827Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-08-3014
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Funding
- NCI NIH HHS [R01 CA082683-10, CA14195, CA82683, R01 CA082683, P30 CA014195, P30 CA014195-35S1, T32 CA 09370, T32 CA009370] Funding Source: Medline
- NHGRI NIH HHS [R01 HG004164, R01 HG004164-03] Funding Source: Medline
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The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling. S6 kinase is the best-characterized downstream effector of mTORC1. mTOR signaling complex 2 (mTORC2) has a role in regulating the actin cytoskeleton and activating Akt through S473 phosphorylation. Herein, we show that mTOR is phosphorylated differentially when associated with mTORC1 and mTORC2 and that intact complexes are required for these mTORC-specific mTOR phosphorylations. Specifically, we find that mTORC1 contains mTOR phosphorylated predominantly on S2448, whereas mTORC2 contains mTOR phosphorylated predominantly on S2481. Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Thus, phospho-S2481 on mTOR serves as a bio-marker for intact mTORC2 and its sensitivity to rapamycin. [Cancer Res 2009;69(5):1821-7]
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