ArticleAmerican journal of physiology. Cell physiology2008
Repetitive deformation activates Src-independent FAK-dependent ERK motogenic signals in human Caco-2 intestinal epithelial cells.
Article in American journal of physiology. Cell physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- ZINC40099027 activates human focal adhesion kinase by accelerating the enzymatic activity of the FAK kinase domain.Pharmacology research & perspectives · 2021Article
- Discovery of Novel Small-Molecule FAK Activators Promoting Mucosal Healing.ACS medicinal chemistry letters · 2021Article
- Mechanical Tension Drives Elongational Growth of the Embryonic Gut.Scientific reports · 2018Article
- The role of Src & ERK1/2 kinases in inspiratory resistive breathing induced acute lung injury and inflammation.Respiratory research · 2017Article
- Graded effects of unregulated smooth muscle myosin on intestinal architecture, intestinal motility and vascular function in zebrafish.Disease models & mechanisms · 2016Article
- Tissue Strain Reorganizes Collagen With a Switchlike Response That Regulates Neuronal Extracellular Signal-Regulated Kinase Phosphorylation In Vitro: Implications for Ligamentous Injury and Mechanotransduction.Journal of biomechanical engineering · 2016Article
- Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract.Experimental biology and medicine (Maywood, N.J.) · 2014Review
- Low-intensity pulsed ultrasound promotes chondrogenic progenitor cell migration via focal adhesion kinase pathway.Ultrasound in medicine & biology · 2014Article
- Distraction-induced intestinal growth: the role of mechanotransduction mechanisms in a mouse model of short bowel syndrome.Tissue engineering. Part A · 2014Article
- Mechanically activated Fyn utilizes mTORC2 to regulate RhoA and adipogenesis in mesenchymal stem cells.Stem cells (Dayton, Ohio) · 2013Article
- Intestinal mucosal atrophy and adaptation.World journal of gastroenterology · 2012Review
- Role of RhoA and its effectors ROCK and mDia1 in the modulation of deformation-induced FAK, ERK, p38, and MLC motogenic signals in human Caco-2 intestinal epithelial cells.American journal of physiology. Cell physiology · 2011Article
- Lactobacillus plantarum surface layer adhesive protein protects intestinal epithelial cells against tight junction injury induced by enteropathogenic Escherichia coli.Molecular biology reports · 2011Article
- ILK mediates the effects of strain on intestinal epithelial wound closure.American journal of physiology. Cell physiology · 2011Article
- Article
- Schlafen 3 induction by cyclic strain regulates intestinal epithelial differentiation.American journal of physiology. Gastrointestinal and liver physiology · 2010Article
- Progress in researches about focal adhesion kinase in gastrointestinal tract.World journal of gastroenterology · 2009Review
- Strain matrix-dependently dissociates gut epithelial spreading and motility.The Journal of surgical research · 2009Article
- The effects of mechanical forces on intestinal physiology and pathology.Cellular signalling · 2009Review
- Delineating the signals by which repetitive deformation stimulates intestinal epithelial migration across fibronectin.American journal of physiology. Gastrointestinal and liver physiology · 2009Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Repetitive deformation due to villous motility or peristalsis may support the intestinal mucosa, stimulating intestinal epithelial proliferation under normal circumstances and restitution in injured and inflamed mucosa rich in tissue fibronectin. Cyclic strain enhances Caco-2 and IEC-6 intestinal epithelial cell migration across fibronectin via ERK. However, the upstream mediators of ERK activation are unknown. We investigated whether Src and FAK mediate strain-induced ERK phosphorylation and migration in human Caco-2 intestinal epithelial cells on fibronectin. Monolayers on tissue fibronectin-precoated membranes were subjected to an average 10% repetitive deformation at 10 cycles/min. Phosphorylation of Src-Tyr 418, FAK-Tyr 397-Tyr 576-Tyr 925, and ERK were significantly increased by deformation. The stimulation of wound closure by strain was prevented by Src blockade with PP2 (10 micromol/l) or specific short interfering (si)RNA. Src inhibition also prevented strain-induced FAK phosphorylation at Tyr 397 and Tyr 576 but not FAK-Tyr 925 or ERK phosphorylation. Reducing FAK by siRNA inhibited strain-induced ERK phosphorylation. Transfection of NH2-terminal tyrosine phosphorylation-deficient FAK mutants Y397F, Y576F-Y577F, and Y397F-Y576F-Y577F did not prevent the activation of ERK2 by cyclic strain, but a FAK mutant at the COOH terminal (Y925F) prevented the strain-induced activation of ERK2. Although the Y397F-Y576F-Y577F FAK construct exhibited less basal FAK-Tyr 925 phosphorylation under static conditions, it nevertheless exhibited increased FAK-Tyr 925 phosphorylation in response to strain. These results suggest that repetitive deformation stimulates intestinal epithelial motility across fibronectin in a manner that requires both Src activation and a novel Src-independent FAK-Tyr 925-dependent pathway that activates ERK. This pathway may be an important target for interventions to promote mucosal healing in settings of intestinal ileus or fasting.
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