Regulation of mTOR by mechanically induced signaling events in skeletal muscle.
Mechanical stimuli play a major role in the regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and the quality of life. Although a link between mechanical stimuli and the regulation of muscle mass has been recognized for decades, the mechanisms involved in converting mechanical information into the molecular events that control this process have not been defined. Nevertheless, significant advancements are being made in this field, and it has recently been established that signaling through a rapamycin-sensitive pathway is necessary for mechanically induced growth of skeletal muscle. Since rapamycin is a highly specific inhibitor of a protein kinase called the mammalian target of rapamycin (mTOR), many investigators have concluded that mTOR signaling is necessary for the mechanically induced growth of skeletal muscle. In this review, we have summarized the current knowledge regarding how mechanical stimuli activate mTOR signaling, discussed the newly discovered role of phospholipase D (PLD) and phosphatidic acid (PA) in this pathway, and considered the potential roles of PLD and PA in the mechanical regulation of skeletal muscle mass.
Hornberger
Troy Alan
TA
Department of Bioengineering and Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California, USA.
Sukhija
Kunal Balu
KB
Chien
Shu
S
D000818:Animals; D049109:Cell Proliferation; D006801:Humans; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000187:drug effects; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus