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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

Inhibition of T-cell activation by PIK3IP1

Marie C DeFrances1, Daniel R Debelius, Jing Cheng

  • 1Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

European Journal of Immunology
|June 19, 2012
PubMed

Insights

The PI3K interacting protein 1 (PIK3IP1) inhibits T-cell activation. This study reveals PIK3IP1 is expressed in T cells and negatively regulates their activation and IL-2 production.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The phosphoinositide 3-kinase (PI3K) pathway is crucial for T-cell function.
  • Negative regulators like PTEN, SHIP, and INPP4B are known, but PIK3IP1's role in lymphocytes is uncharacterized.
  • PIK3IP1 is a transmembrane protein that inhibits PI3K activation by blocking p85 adaptor protein binding to p110.

Purpose of the Study:

  • To investigate the role of PIK3IP1 in T-cell development and activation.
  • To determine if PIK3IP1 expression affects T-cell signaling pathways.

Main Methods:

  • Assessed PIK3IP1 expression in T cells.
  • Utilized ectopic PIK3IP1 expression in Jurkat and D10 T-cell lines to observe effects on NFAT/AP-1 reporter activity.
  • Employed siRNA-mediated silencing of PIK3IP1 in T-cell lines to analyze Akt phosphorylation, T-cell activation, and IL-2 production.

Main Results:

  • PIK3IP1 is expressed in T cells.
  • Overexpression of PIK3IP1 suppressed T-cell activation reporter activity.
  • PIK3IP1 knockdown enhanced Akt phosphorylation, T-cell activation, and IL-2 production.

Conclusions:

  • PIK3IP1 is a novel negative regulator of T-cell activation.
  • PIK3IP1 functions to inhibit key signaling events leading to T-cell activation and cytokine production.

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