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Modulation of proximal signaling in normal and transformed B cells by transmembrane adapter Cbp/PAG

Maria E Kalland1, Silje A Solheim, Sigrid S Skånland

  • 1The Biotechnology Centre of Oslo, Nordic EMBL Partnership, University of Oslo, P.O. Box 1125 Blindern, N-0317 Oslo, Norway.

Experimental Cell Research
|June 5, 2012
PubMed

Insights

Cbp/PAG acts as a negative regulator in B cell receptor signaling. Reduced Cbp/PAG levels enhance proximal signaling, while its over-expression dampens calcium flux in B cells.

Area of Science:

  • Immunology
  • Cell Signaling
  • Molecular Biology

Background:

  • Cbp/PAG (Csk binding protein/phospho-protein associated with glycosphingolipid-enriched microdomains) is a transmembrane protein.
  • Cbp/PAG negatively regulates T cell activation by adapting C-terminal Src kinase (Csk).
  • In T cells, Cbp/PAG binding to phosphorylated FynT (pTyr317) facilitates Csk targeting to lipid rafts.

Purpose of the Study:

  • To investigate the role of Cbp/PAG in early B cell receptor (BCR) signaling.
  • To explore a potential parallel function for Cbp/PAG and Lyn kinase in BCR signaling.
  • To compare BCR-triggered signaling profiles in normal and transformed B cells.

Main Methods:

  • Utilized phospho-specific flow cytometry to analyze BCR-triggered responses.
  • Compared signal profiles in normal and transformed B cells.
  • Manipulated Cbp/PAG levels through reduction and over-expression in B cells.

Main Results:

  • Reduced Cbp/PAG levels in human normal B cells resulted in enhanced and prolonged activation of proximal signaling mediators.
  • Over-expression of Cbp/PAG in normal, EBV-transformed B cells led to reduced calcium flux.
  • These findings indicate Cbp/PAG's involvement in modulating early BCR signaling pathways.

Conclusions:

  • Cbp/PAG exhibits a negative regulatory function in proximal B cell receptor signaling.
  • The adapter protein Cbp/PAG plays a critical role in controlling the amplitude and duration of BCR-mediated signals.
  • Understanding Cbp/PAG's role is crucial for comprehending B cell activation and potential therapeutic targets.

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