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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
Evidence for two distinct phosphorylation pathways activated by high affinity immunoglobulin E receptors
M Adamczewski1, R Paolini, J P Kinet
1Molecular Allergy and Immunology Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852.
The Journal of Biological Chemistry
|September 5, 1992
Summary
Phenylarsine oxide disrupts IgE receptor signaling by blocking a specific pathway required for phospholipase C-gamma 1 phosphorylation and activation. This reveals distinct signaling pathways activated by receptor aggregation, impacting mast cell functions.
Area of Science:
- Immunology
- Cell Signaling
- Biochemistry
Background:
- The high-affinity IgE receptor (FcεRI) on mast cells lacks intrinsic kinase activity but activates downstream kinases.
- Receptor engagement initiates signaling cascades involving protein phosphorylation, calcium influx, and cellular activation.
Purpose of the Study:
- To investigate the role of phenylarsine oxide (PAO) in IgE receptor-mediated signaling.
- To elucidate the specific pathways affected by PAO in mast cell activation.
Main Methods:
- Treatment of mast cells with PAO, a tyrosine phosphatase inhibitor.
- Analysis of IgE receptor phosphorylation, phospholipase C (PLC) phosphorylation, intracellular calcium levels, and serotonin release.
Main Results:
- PAO uncoupled IgE receptor signaling from phosphatidylinositol metabolism, calcium increase, and serotonin release.
- PAO did not inhibit receptor- or substrate-phosphorylating kinases or phosphatases involved in dephosphorylation.
- PAO specifically inhibited the phosphorylation of phospholipase C-gamma 1 (PLCγ1) without affecting its in vitro activity.
Conclusions:
- Receptor aggregation activates at least two distinct phosphorylation pathways: one insensitive to PAO and another sensitive pathway crucial for PLCγ1 phosphorylation.
- A PAO-sensitive element is required for the phosphorylation and activation of PLCγ1, linking IgE receptor engagement to downstream cellular responses.
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