Epidermal growth factor activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases

Christopher L. Wolfgang, Cheng Mao Lin, Qing He Meng, Anne M. Karinch, Thomas C. Vary, Ming Pan

Research output: Contribution to journalArticlepeer-review

Abstract

Glutamine is an essential nutrient for gut functions, but the regulation of its uptake by intestinal mucosal cells is poorly understood. Given the pivotal role of epidermal growth factor (EGF) in regulating gut metabolism, growth, and differentiation, this in vitro study was designed to investigate the intracellular signaling pathways involved in the regulation of EGF-mediated intestinal glutamine transport in intestinal epithelia. Continuous incubation with EGF (>30 hours, 100 ng/ml) stimulated glutamine transport activity across intestinal epithelial Caco-2 cell apical membrane. Exposure to EGF for 48 hours resulted in an increase in transport activity (50%) and glutamine transport system B gene ATB0 mRNA levels (ninefold). EGF stimulated glutamine transport activity by increasing the glutamine transporter maximal velocity (Vmax) without altering the transporter apparent affinity (Km). Furthermore, EGF stimulated both intracellular protein kinase C and mitogen-activated protein kinase MEK1/2 activities. The EGF-stimulated glutamine transport activity was attenuated individually by the specific protein kinase C inhibitor chelerythrine chloride and the mitogen-activated protein kinase MEK1 inhibitor PD 98059. These data suggest that EGF activates glutamine transport activity across intestinal epithelial membrane via a signaling mechanism that involves activation of protein kinase C and the mitogen-activated protein kinase MEK1/2 cascade. EGF activates glutamine transport via alterations in transporter mRNA levels and the number of functional copies of transporter units.

Original languageEnglish (US)
Pages (from-to)149-156
Number of pages8
JournalJournal of Gastrointestinal Surgery
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Keywords

  • Epidermal growth factor
  • Glutamine
  • Intestine
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Surgery
  • Gastroenterology

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