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REDD2 inhibits mTOR signaling in skeletal muscle cells
Author(s) -
Miyazaki Mitsunori,
McCarthy John J,
Zhang Xiping,
Esser Karyn A
Publication year - 2008
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.22.1_supplement.959.13
Subject(s) - pi3k/akt/mtor pathway , rheb , rptor , protein kinase b , microbiology and biotechnology , autophagy , skeletal muscle , mtorc2 , mechanistic target of rapamycin , signal transduction , myocyte , kinase , chemistry , c2c12 , mtorc1 , cell growth , p70 s6 kinase 1 , tsc2 , biology , endocrinology , myogenesis , biochemistry , apoptosis
The protein kinase mTOR (mammalian target of rapamycin) is established in skeletal muscle as a key signaling hub during cell growth/hypertrophy. In this study, we determined that the stress responsive gene REDD2 inhibits mTOR signaling in skeletal muscle cells. The effects of REDD2 expression on mTOR activity were also determined in C2C12 muscle cell. Overexpression of REDD2 resulted in decreased mTOR kinase activity under both basal and amino acid‐stimulated conditions. These inhibitory effects on mTOR signaling are mediated downstream of Akt but upstream of Rheb. Knock down of TSC2 (tuberous sclerosis complex 2) using siRNA potently activated mTOR signaling and was sufficient to rescue REDD2 inhibition of mTOR activity. Consistent with the in vitro studies, REDD2 mRNA levels are rapidly reduced in the plantaris muscle during hypertrophy and increased in vivo during atrophic conditions. These results indicate that REDD2 negatively regulates mTOR activity likely through modulation of TSC2 function and regulating of REDD2 might regulation of muscle cell size in mice. This study is supported by the grant provided from National Institute of Health (AR45617).