Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells
Year: 2006
Type: article
Abstract: 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.
Source: Blood
Authors: 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, Wahn Soo Choi
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W2126247006