Cited by 55Digestive system and related healthWound Healing and TreatmentsGastrointestinal motility and disorders

Vangl1 Protein Acts as a Downstream Effector of Intestinal Trefoil Factor (ITF)/TFF3 Signaling and Regulates Wound Healing of Intestinal Epithelium

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Kalabis, Jiri, Rosenberg, Ian, Podolsky, Daniel K.·2006·Journal of Biological Chemistry

Abstract

The intestinal trefoil factor (ITF/TFF3) protects intestinal epithelia from a range of insults and contributes to mucosal repair. However, the signaling events that mediate healing responses are only partially understood. To identify ITF signaling pathways, proteins that were Ser/Thr phosphorylated in response to ITF stimulation were immunoprecipitated from human colon carcinoma cell lines and identified by mass spectrometry. We demonstrated that Van Gogh-like protein 1 (also designated Vang-like 1 or Vangl1), a protein with four transmembrane domains, was Ser/Thr phosphorylated in response to ITF stimulation. Vangl1 was present in normal human colon and all intestinal epithelial cell lines (IEC) tested. In transfected IEC, FLAG-Vangl1 was mostly present in the Nonidet P-40 soluble fraction as detected by Western blotting, corresponding to the localization of endogenous protein in cytoplasmic vesicular structures by confocal microscopy with rabbit polyclonal anti-human Vangl1 antibody (alpha-Vangl1). Vangl1 cell membrane association increased with differentiation, as demonstrated by co-localization with E-cadherin in differentiated IEC. Increased Vangl1 phosphorylation after stimulation with ITF corresponded to decreased cell membrane association with E-cadherin. Functionally, Vangl1 overexpression enhanced ITF unstimulated and stimulated wound closure of IEC, whereas siRNA directed against Vangl1 inhibited the migratory response to ITF. Vangl1 protein may serve as an effector mediating the ITF healing response of the intestinal mucosa.

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  1. Suemori, S., Lynch-Devaney, K., and Podolsky, D. K. (1991) Proc. Natl. Acad. Sci.
  2. Taupin, D. R., Kinoshita, K., and Podolsky, D. K. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 799 -804

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Authors
Kalabis, J., Rosenberg, I., & Podolsky, D. K.
Affiliations
Harvard University (US)
Corresponding author
Podolsky, Daniel K.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2006-03
Volume
281
Issue
10
Pages
6434-6441
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2047747244
Cited by
55
References
32
Citations by year
2025: 2 · 2024: 3 · 2023: 1 · 2022: 1 · 2020: 2 · 2019: 2 · 2017: 1 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 5 · 2012: 5
FWCI
1.89
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Massachusetts General Hospital
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK046906, P30DK043351)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
Vangl1, TFF3, mucosal healing, E-cadherin, cell membrane association, cell migration, intestinal epithelial differentiation, colon cancer cell lines
MeSH terms
Trefoil Factor-2, Trefoil Factor-3, Animals, Carrier Proteins, Cell Movement, Chlorocebus aethiops, Humans, Intestinal Mucosa, Membrane Proteins, Peptides, Phosphorylation, RNA, Messenger, Serine, Threonine, Wound Healing, Signal Transduction, DNA, Complementary, Caco-2 Cells, HT29 Cells, COS Cells, HCT116 Cells

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