Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through tyrosine phosphorylation of villin

Narendra Kumar, Jayshree Mishra, Vishal S. Narang, Christopher Waters

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Janus kinase 3 (Jak3) is a non-receptor tyrosine kinase known to be expressed in hematopoietic cells. Studies of whole organ homogenates show that Jak3 is also expressed in the intestines of both human and mice. However, neither its expression nor its function has been defined in intestinal epithelial enterocytes. The present studies demonstrate that functional Jak3 is expressed in human intestinal enterocytes HT-29 Cl-19A and Caco-2 and plays an essential role in the intestinal epithelial wound repair process in response to interleukin 2 (IL-2). Exogenous IL-2 enhanced the wound repair of intestinal enterocytes in a dose-dependent manner. Activation by IL-2 led to rapid tyrosine phosphorylation and redistribution of Jak3. IL-2-stimulated redistribution of Jak3 was inhibited by the Jak3-specific inhibitor WHI-P131. IL-2 also induced Jak3-dependent redistribution of the actin cytoskeleton in migrating cells. In these cells Jak3 interacted with the intestinal and renal epithelial cell-specific cytoskeletal protein villin in an IL-2-dependent manner. Inhibition of Jak3 activation resulted in loss of tyrosine phosphorylation of villin and a significant decrease in wound repair of the intestinal epithelial cells. Previously, we had shown that tyrosine phosphorylation of villin is important for cytoskeletal remodeling and cell migration. The present study demonstrates a novel pathway in intestinal enterocytes in which IL-2 enhances intestinal wound repair through mechanisms involving Jak3 and its interactions with villin.

Original languageEnglish (US)
Pages (from-to)30341-30345
Number of pages5
JournalJournal of Biological Chemistry
Volume282
Issue number42
DOIs
StatePublished - Oct 19 2007

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Janus Kinase 3
Phosphorylation
Interleukin-2
Tyrosine
Repair
Wounds and Injuries
Enterocytes
Epithelial Cells
Chemical activation
villin
Cytoskeletal Proteins
Actin Cytoskeleton
Protein-Tyrosine Kinases
Intestines
Cell Movement
Actins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through tyrosine phosphorylation of villin. / Kumar, Narendra; Mishra, Jayshree; Narang, Vishal S.; Waters, Christopher.

In: Journal of Biological Chemistry, Vol. 282, No. 42, 19.10.2007, p. 30341-30345.

Research output: Contribution to journalArticle

Kumar, Narendra ; Mishra, Jayshree ; Narang, Vishal S. ; Waters, Christopher. / Janus kinase 3 regulates interleukin 2-induced mucosal wound repair through tyrosine phosphorylation of villin. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 42. pp. 30341-30345.
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