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Blood, 1 August 2006, Vol. 108, No. 3, pp. 956-964.
Prepublished online as a Blood First Edition Paper on March 30, 2006; DOI 10.1182/blood-2005-10-009159.
 Previous Article | Next Article 
Submitted October 6, 2005
Accepted March 10, 2006
Phospholipase D2 acts as an essential adaptor protein in
the activation of Syk in antigen-stimulated mast cells
Jun Ho Lee, Young Mi Kim, Nam Wook Kim, Jie Wan Kim, Erk Her, Bo Kyung Kim, Jong Hyun Kim, Sung Ho Ryu, Jong Woo Park, Dong Wan Seo, Jeung Whan Han, Michael A Beaven, and Wahn Soo Choi*
Department of Immunology, Konkuk University, Chungju, Korea
College of Pharmacy, Duksung Women's University, Seoul, Korea
Department of Physiology, College of Medicine, Konkuk University, Chungju, Korea
Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Korea
Pohang University of Science and Technology
College of Pharmacy, Sungkyunkwan University, Suwon, Korea
Laboratory of Molecular Immunology, National, Heart, Lung, and Blood Institute, NIH, Bethesda, MD
* Corresponding author; email: wahnchoi{at}kku.ac.kr.
Mast cells are responsible for IgE-mediated allergic
reactions. Phospholipase (PL) D1 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 co-localization of Syk with PLD2 on the plasma
membrane as indicated by co-immunoprecipitation 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.
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