Role of mTOR signaling in intestinal cell migration
- 1 September 2006
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 291 (3), G510-G517
- https://doi.org/10.1152/ajpgi.00189.2005
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 (p70s6k), 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/p70s6k pathway inhibitors (rapamycin, wortmannin, and intracellular Ca2+ chelation) inhibit cell migration, 3) ARG activates migration and mTOR/p70s6k (but not ERK-2) in migrating enterocytes, and 4) immunocytochemistry reveals abundant p70s6k staining in cytoplasm, whereas phospho-p70s6k is virtually all intranuclear in resting cells but redistributes to the periphery on activation by ARG. We conclude that mTOR/p70s6k 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.Keywords
This publication has 34 references indexed in Scilit:
- Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanismGut, 2004
- Role of the p70S6K pathway in regulating the actin cytoskeleton and cell migrationExperimental Cell Research, 2004
- Intracellular Sensing of Amino Acids in Xenopus laevis Oocytes Stimulates p70 S6 Kinase in a Target of Rapamycin-dependent MannerJournal of Biological Chemistry, 2002
- Among translational effectors, p70S6k is uniquely sensitive to inhibition by glucocorticoidsBiochemical Journal, 2000
- Ribosomal S6 Kinase Signaling and the Control of TranslationExperimental Cell Research, 1999
- Brief report. Relationship between nutritional status and histologic findings in small bowel mucosa of children presenting with diarrhoea of more than 14 days' durationJournal of Tropical Pediatrics, 1999
- Amino Acid-dependent Control of p70s6kPublished by Elsevier BV ,1999
- An Intracellular Calcium Signal Activates p70 but Not p90 Ribosomal S6 Kinase in Liver Epithelial CellsJournal of Biological Chemistry, 1997
- Cell Cycle Regulation of p70 S6 Kinase and p42/p44 Mitogen-activated Protein Kinases in Swiss Mouse 3T3 FibroblastsPublished by Elsevier BV ,1996
- Glutamine Is Essential for Epidermal Growth Factor‐Stimulated Intestinal Cell ProliferationJournal of Parenteral and Enteral Nutrition, 1994