Epithelial cell kinase-B61: An autocrine loop modulating intestinal epithelial migration and barrier function

Ian M. Rosenberg, Michael Göke, Michiyuki Kanai, Hans Christian Reinecker, Daniel K. Podolsky

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Epithelial cell kinase (Eck) is a member of a large family of receptor tyrosine kinases whose functions remain largely unknown. Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2. Immunocytochemical staining demonstrated coexpression of Eck and B61 in the same cells, suggestive of an autocrine loop. Eck levels were maximal in preconfluent cells. In contrast, B61 levels were barely detectable in preconfluent cells and increased progressively after the cells reached confluence. Caco-2 cells cultured in the presence of added B61 showed a significant reduction in the levels of dipeptidyl peptidase and sucrase-isomaltase mRNA, markers of Caco-2 cell differentiation. Cytokines interleukin-1β (IL-1β), basic fibroblast growth factor, IL-2, epidermal growth factor, and transforming growth factor-β modulated steady-state levels of Eck and B61 mRNA and regulated Eck activation as assessed by tyrosine phosphorylation. Functionally, stimulation of Eck by B61 resulted in increased proliferation, enhanced barrier function, and enhanced restitution of injured epithelial monolayers. These results suggest that the Eck-B61 interaction, a target of regulatory peptides, plays a role in intestinal epithelial cell development, migration, and barrier function, contributing to homeostasis and preservation of continuity of the epithelial barrier.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number4 36-4
StatePublished - 1997

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Phosphotransferases
Epithelial Cells
Caco-2 Cells
Fibroblast Growth Factor 2
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Oligo-1,6-Glucosidase
Sucrase
Messenger RNA
Receptor Protein-Tyrosine Kinases
Transforming Growth Factors
Interleukin-1
Epidermal Growth Factor
Cell Movement
Interleukin-2
Tyrosine
Cell Differentiation
Adenocarcinoma
Homeostasis
Phosphorylation
Staining and Labeling

Keywords

  • Cytokines
  • Differentiation
  • Growth factors
  • Receptors

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Epithelial cell kinase-B61 : An autocrine loop modulating intestinal epithelial migration and barrier function. / Rosenberg, Ian M.; Göke, Michael; Kanai, Michiyuki; Reinecker, Hans Christian; Podolsky, Daniel K.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 273, No. 4 36-4, 1997.

Research output: Contribution to journalArticle

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AU - Podolsky, Daniel K.

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