title: Role of mTOR signaling in intestinal cell migration.
abstract: An early signaling event activated by amino acids and growth factors in many cell types is the phosphorylation of the mammalian target of rapamycin (mTOR; FRAP), which is functionally linked to ribosomal protein s6 kinase (p70(s6k)), a kinase that plays a critical regulatory role in the translation of mRNAs and protein synthesis. We previously showed that intestinal cell migration, the initial event in epithelial restitution, is enhanced by l-arginine (ARG). In this study, we used amino acids as prototypic activators of mTOR and ARG, IGF-1, or serum as recognized stimulators of intestinal cell migration. We found that 1) protein synthesis is required for intestinal cell migration, 2) mTOR/p70(s6k) pathway inhibitors (rapamycin, wortmannin, and intracellular Ca(2+) chelation) inhibit cell migration, 3) ARG activates migration and mTOR/p70(s6k) (but not ERK-2) in migrating enterocytes, and 4) immunocytochemistry reveals abundant p70(s6k) staining in cytoplasm, whereas phospho-p70(s6k) is virtually all intranuclear in resting cells but redistributes to the periphery on activation by ARG. We conclude that mTOR/p70(s6k) signaling is essential to intestinal cell migration, is activated by ARG, involves both nuclear and cytoplasmic events, and may play a role in intestinal repair.
authors.affiliation: Div. of Gastroenterology, Dept. of Pediatrics, Univ. of Texas Medical School at Houston, 6431 Fannin St., MSB 7.137, Houston, TX 77030, USA. J.Marc.Rhoads@uth.tmc.edu
authors.forename: J Marc
authors.initials: JM
authors.lastname: Rhoads
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Niu
authors.forename: Jack
authors.initials: J
authors.lastname: Odle
authors.forename: Lee M
authors.initials: LM
authors.lastname: Graves
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000502:physiology*; D007422:Intestines / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D001120:Arginine; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases