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Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
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Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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p85beta phosphoinositide 3-kinase regulates CD28 coreceptor function.

Isabela Alcázar1, Isabel Cortés, Angel Zaballos

  • 1Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Madrid, Spain.

Blood
|February 5, 2009
PubMed
Summary

The p85beta protein is crucial for CD28 receptor function in T cells, regulating immune responses and memory formation. Its absence impairs T cell differentiation and secondary immune responses.

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

Published on: January 22, 2019

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • CD28 receptor on T cells is vital for immune memory.
  • CD28 regulates T cell activation by modulating CBL ubiquitin ligases.
  • The role of PI3K regulatory subunit p85beta in CD28 function is unclear.

Purpose of the Study:

  • To investigate the role of p85beta in CD28-mediated T cell activation and differentiation.
  • To determine the binding affinity of p85beta to CD28 and CBL compared to p85alpha.

Main Methods:

  • Studied T cells lacking p85beta.
  • Assessed CD28-induced intracellular signaling events.
  • Analyzed T cell differentiation and secondary immune responses.

Main Results:

  • p85beta binds to CD28 and CBL with higher affinity than p85alpha.
  • Deletion of p85beta disrupts CD28-mediated down-regulation of CBL and CBL-b.
  • p85beta deficiency impairs PI3K pathway activation and T cell differentiation.
  • T cells lacking p85beta show defective secondary immune responses.

Conclusions:

  • p85beta is essential for CD28 signaling and T cell differentiation.
  • p85beta plays a key role in mounting efficient secondary immune responses.
  • p85beta is involved in CD28-mediated activation and differentiation of antigen-stimulated T cells.