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Epidermal growth factor-stimulated intestinal epithelial cell migration requires Src family kinase-dependent p38 MAPK signaling.
J Biol Chem. 2004 Oct 22; 279(43):44513-21.JB

Abstract

Members of the epidermal growth factor (EGF) family of ligands and their receptors regulate migration and growth of intestinal epithelial cells. However, our understanding of the signal transduction pathways determining these responses is incomplete. In this study we tested the hypothesis that p38 is required for EGF-stimulated intestinal epithelial monolayer restitution. EGF-stimulated migration in a wound closure model required continuous presence of ligand for several hours for maximal response, suggesting a requirement for sustained signal transduction pathway activation. In this regard, prolonged exposure of cells to EGF activated p38 for up to 5 h. Furthermore genetic or pharmacological blockade of p38 signaling inhibited the ability of EGF to accelerate wound closure. Interestingly p38 inhibition was associated with increased EGF-stimulated ERK1/ERK2 phosphorylation and cell proliferation, suggesting that p38 regulates the balance of proliferation/migration signaling in response to EGF receptor activity. Activation of p38 in intestinal epithelial cells through EGF receptor was abolished by blockade of Src family tyrosine kinase signaling but not inhibition of phosphatidylinositol 3-kinase or protein kinase C. Taken together, these data suggest that Src family kinase-dependent p38 activation is a key component of a signaling switch routing EGF-stimulated responses to epithelial cell migration/restitution rather than proliferation during wound closure.

Authors+Show Affiliations

Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2576, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15316018

Citation

Frey, Mark R., et al. "Epidermal Growth Factor-stimulated Intestinal Epithelial Cell Migration Requires Src Family Kinase-dependent P38 MAPK Signaling." The Journal of Biological Chemistry, vol. 279, no. 43, 2004, pp. 44513-21.
Frey MR, Golovin A, Polk DB. Epidermal growth factor-stimulated intestinal epithelial cell migration requires Src family kinase-dependent p38 MAPK signaling. J Biol Chem. 2004;279(43):44513-21.
Frey, M. R., Golovin, A., & Polk, D. B. (2004). Epidermal growth factor-stimulated intestinal epithelial cell migration requires Src family kinase-dependent p38 MAPK signaling. The Journal of Biological Chemistry, 279(43), 44513-21.
Frey MR, Golovin A, Polk DB. Epidermal Growth Factor-stimulated Intestinal Epithelial Cell Migration Requires Src Family Kinase-dependent P38 MAPK Signaling. J Biol Chem. 2004 Oct 22;279(43):44513-21. PubMed PMID: 15316018.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal growth factor-stimulated intestinal epithelial cell migration requires Src family kinase-dependent p38 MAPK signaling. AU - Frey,Mark R, AU - Golovin,Anastasia, AU - Polk,D Brent, Y1 - 2004/08/16/ PY - 2004/8/19/pubmed PY - 2004/12/16/medline PY - 2004/8/19/entrez SP - 44513 EP - 21 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 279 IS - 43 N2 - Members of the epidermal growth factor (EGF) family of ligands and their receptors regulate migration and growth of intestinal epithelial cells. However, our understanding of the signal transduction pathways determining these responses is incomplete. In this study we tested the hypothesis that p38 is required for EGF-stimulated intestinal epithelial monolayer restitution. EGF-stimulated migration in a wound closure model required continuous presence of ligand for several hours for maximal response, suggesting a requirement for sustained signal transduction pathway activation. In this regard, prolonged exposure of cells to EGF activated p38 for up to 5 h. Furthermore genetic or pharmacological blockade of p38 signaling inhibited the ability of EGF to accelerate wound closure. Interestingly p38 inhibition was associated with increased EGF-stimulated ERK1/ERK2 phosphorylation and cell proliferation, suggesting that p38 regulates the balance of proliferation/migration signaling in response to EGF receptor activity. Activation of p38 in intestinal epithelial cells through EGF receptor was abolished by blockade of Src family tyrosine kinase signaling but not inhibition of phosphatidylinositol 3-kinase or protein kinase C. Taken together, these data suggest that Src family kinase-dependent p38 activation is a key component of a signaling switch routing EGF-stimulated responses to epithelial cell migration/restitution rather than proliferation during wound closure. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15316018/Epidermal_growth_factor_stimulated_intestinal_epithelial_cell_migration_requires_Src_family_kinase_dependent_p38_MAPK_signaling_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15316018 DB - PRIME DP - Unbound Medicine ER -