Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells

Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted...

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Published in:Blood 2006-08, Vol.108 (3), p.956-964
Main Authors: Lee, Jun Ho, Kim, Young Mi, Kim, Nam Wook, Kim, Jie Wan, Her, Erk, Kim, Bo Kyung, Kim, Jong Hyun, Ryu, Sung Ho, Park, Jong Woo, Seo, Dong Wan, Han, Jeung Whan, Beaven, Michael A., Choi, Wahn Soo
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Adaptor Proteins, Signal Transducing - physiology
Allergic diseases
Animals
Antigens - physiology
Binding Sites
Biological and medical sciences
Cell Degranulation
Cell Line
General aspects
Immunobiology
Immunopathology
Intracellular Signaling Peptides and Proteins - metabolism
Mast Cells - enzymology
Mast Cells - immunology
Mast Cells - metabolism
Medical sciences
Phospholipase D - metabolism
Phospholipase D - physiology
Phosphorylation
Protein Binding
Protein-Tyrosine Kinases - metabolism
Rats
Syk Kinase
Transfection
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Summary:Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted in increased association and colocalization of Syk with PLD2 on the plasma membrane as indicated by coimmunoprecipitation and confocal microscopy. This association was dependent on tyrosine phosphorylation of Syk but not on PLD2 activity. In vitro, PLD2 interacted via its Phox homology (PX) domain with recombinant Syk to induce phosphorylation and activation of Syk. Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R enhanced antigen-induced phosphorylations of Syk and its downstream targets, the adaptor proteins LAT and SLP-76, while expression of a PLD2 siRNA blocked these phosphorylations. Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2005-10-009159