Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration

Jason D. Matthews, Ronen Sumagin, Benjamin H. Hinrichs, Asma Nusrat, Charles A. Parkos, Andrew S. Neish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Intestinal wounds often occur during inflammatory and ischemic disorders of the gut. To repair damage, intestinal epithelial cells must rapidly spread and migrate to cover exposed lamina propria, events that involve redox signaling. Wounds are subject to extensive redox alterations, particularly resulting from H2O2 produced in the adjacent tissue by both the epithelium and emigrating leukocytes. The mechanisms governing these processes are not fully understood, particularly at the level of protein signaling. Crk-associated substrate, or Cas, is an important signaling protein known to modulate focal adhesion and actin cytoskeletal dynamics, whose association with Crk is regulated by Abl kinase, a ubiquitously expressed tyrosine kinase. We sought to evaluate the role of Abl regulation of Cas at the level of cell spreading and migration during wound closure. As a model, we used intestinal epithelial cells exposed to H2O2 or scratch wounded to assess the Abl-Cas signaling pathway. We characterized the localization of phosphorylated Cas in mouse colonic epithelium under baseline conditions and after biopsy wounding the mucosa. Analysis of actin and focal adhesion dynamics by microscopy or biochemical analysis after manipulating Abl kinase revealed that Abl controls redox-dependent Cas phosphorylation and localization to influence cell spreading and migration. Collectively, our data shed new light on redox-sensitive protein signaling modules controlling intestinal wound healing.

Original languageEnglish (US)
Pages (from-to)G458-G465
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume311
Issue number3
DOIs
StatePublished - 2016

Keywords

  • Cytoskeleton
  • Focal adhesions
  • Reactive oxygen species
  • Restitution

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Redox control of Cas phosphorylation requires Abl kinase in regulation of intestinal epithelial cell spreading and migration'. Together they form a unique fingerprint.

Cite this