Related Experiment Video

Updated: Feb 24, 2026

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry
10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

7.7K

T cell protein tyrosine phosphatase prevents STAT1 induction of claudin-2 expression in intestinal epithelial cells

Moorthy Krishnan1, Declan F McCole1

  • 1Division of Biomedical Sciences, University of California, Riverside, California.

Annals of the New York Academy of Sciences
|August 15, 2017
PubMed

Insights

T cell protein tyrosine phosphatase (TCPTP) protects the intestinal barrier by limiting claudin-2 expression via STAT1 signaling. Loss of TCPTP function may worsen inflammatory bowel disease by disrupting this barrier.

Area of Science:

  • Molecular biology
  • Cell biology
  • Immunology

Background:

  • The intestinal epithelium forms a selective barrier regulated by tight junctions (TJs).
  • Claudin-2 is a TJ protein that increases intestinal permeability and reduces transepithelial electrical resistance (TER).
  • Interferon-gamma (IFN-γ), a proinflammatory cytokine, activates JAK-STAT signaling and can increase claudin-2 expression.

Purpose of the Study:

  • To investigate the role of T cell protein tyrosine phosphatase (TCPTP) in regulating intestinal epithelial barrier function.
  • To elucidate the mechanism by which TCPTP deficiency affects claudin-2 expression and barrier integrity.
  • To determine the involvement of STAT1 signaling in TCPTP-mediated regulation of claudin-2.

Main Methods:

  • Utilized TCPTP-deficient epithelial cells and transient knockdown (KD) of TCPTP and STAT1.
  • Measured transepithelial electrical resistance (TER) to assess barrier function.
  • Analyzed claudin-2 expression, STAT1 activation, and STAT1 binding to the CLDN2 promoter.
  • Employed site-directed mutagenesis of the STAT-binding site in the CLDN2 promoter.

Main Results:

  • Decreased TER in TCPTP-deficient cells was alleviated by STAT1 KD.
  • Increased claudin-2 expression in TCPTP-deficient cells required enhanced STAT1 activation and binding to the CLDN2 promoter.
  • Mutation of the STAT-binding site prevented elevated CLDN2 promoter activity in TCPTP-deficient cells.

Conclusions:

  • TCPTP protects the intestinal epithelial barrier by restricting STAT-induced claudin-2 expression.
  • Loss-of-function mutations in TCPTP may contribute to intestinal barrier defects in chronic inflammatory diseases.
  • TCPTP acts as a negative regulator of STAT1-mediated claudin-2 expression in the intestinal epithelium.
Keywords:
barrier functioninflammatory bowel diseaseinterferon-γprotein tyrosine phosphatasetight junction

More Related Videos

Three-Dimensional Culture of Murine Colonic Crypts to Study Intestinal Stem Cell Function Ex Vivo07:46

Three-Dimensional Culture of Murine Colonic Crypts to Study Intestinal Stem Cell Function Ex Vivo

Published on: October 11, 2022

4.1K
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.7K

Related Concept Videos

Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.5K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.7K
Tight Junctions01:29

Tight Junctions

Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
7.9K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
13.3K
Renewal of Intestinal Stem Cells01:23

Renewal of Intestinal Stem Cells

The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
3.4K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.3K