Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells
Open Access
- 1 August 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (3) , 956-964
- https://doi.org/10.1182/blood-2005-10-009159
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.Keywords
This publication has 75 references indexed in Scilit:
- The uncovering of a novel regulatory mechanism for PLD2: Formation of a ternary complex with protein tyrosine phosphatase PTP1B and growth factor receptor-bound protein GRB2Biochemical and Biophysical Research Communications, 2005
- Activation of RBL-2H3 Mast Cells Is Dependent on Tyrosine Phosphorylation of Phospholipase D2 by Fyn and FgrMolecular and Cellular Biology, 2004
- Transmodulation between Phospholipase D and c-Src Enhances Cell ProliferationMolecular and Cellular Biology, 2003
- Collapsin Response Mediator Protein-2 Inhibits Neuronal Phospholipase D2 Activity by Direct InteractionPublished by Elsevier ,2002
- Structural basis for syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptideJournal of Molecular Biology, 1998
- Phospholipase D1 localises to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulationCurrent Biology, 1998
- Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganizationCurrent Biology, 1997
- Identification of the major sites of autophosphorylation of the murine protein-tyrosine kinase SykBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1997
- Antigen-induced biphasic diacylglycerol formation in RBL-2H3 cells: The late sustained phase due to phosphatidylcholine hydrolysis is dependent on protein kinase CBiochemical and Biophysical Research Communications, 1991
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970