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Transmembrane signalling and paf-acether biosynthesis.

E Ninio1, F Joly

  • 1Institut National de la Santé et de la Recherche Médical U200, Clamart, France.

Lipids
|December 1, 1991
PubMed
Summary
This summary is machine-generated.

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Platelet-activating factor (PAF) biosynthesis is controlled by acetyltransferase activation, likely via phosphorylation. This process is crucial in inflammatory cells like neutrophils and mast cells.

Area of Science:

  • Immunology and Cell Biology
  • Biochemistry and Molecular Biology

Background:

  • Platelet-activating factor (PAF) is a potent lipid mediator involved in inflammatory responses.
  • The enzyme lyso-PAF-acether (lyso-PAF):acetyl-CoA acetyltransferase regulates PAF biosynthesis.
  • Acetyltransferase activation is a key step in PAF production within proinflammatory cells.

Purpose of the Study:

  • To investigate the mechanisms controlling acetyltransferase activation and PAF biosynthesis.
  • To explore the roles of different signaling pathways and kinases in PAF production.
  • To compare PAF formation in different cell types, including human neutrophils and murine mast cells.

Main Methods:

  • Analysis of acetyltransferase expression and activation in response to specific agonists.
  • Investigation of post-translational modifications, particularly phosphorylation, of the acetyltransferase precursor.

Related Experiment Videos

  • Stimulation of human neutrophils and murine mast cells with phorbol myristate acetate (PMA) and diacylglycerol to assess PAF production.

    • Main Results:

    • Acetyltransferase activation, a rate-limiting step in PAF biosynthesis, is controlled by agonists.
    • Activation involves post-translational modification, likely phosphorylation catalyzed by cAMP-dependent kinase, with potential calcium/calmodulin-dependent kinase involvement.
    • Human neutrophils, unlike murine mast cells, produce PAF upon stimulation with PMA or diacylglycerol; acetyltransferase is activated by PMA in both cell types.

    Conclusions:

    • Acetyltransferase activation is a critical regulatory point for PAF biosynthesis in inflammatory cells.
    • Phosphorylation is the primary mechanism for acetyltransferase activation, with potential roles for specific kinases.
    • Further research is needed to clarify the specific signaling pathways, including PKC and GTP-regulated proteins, involved in PAF formation.