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- Title
Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of the RBL-2H3 leukemic mast cell line.
- Authors
Anfossi, Nicolas; Lucas, Mathias; Diefenbach, Andreas; Bühring, Hans-Jörg; Raulet, David; Tomasello, Elena; Vivier, Eric
- Abstract
A common feature of hematopoietic activating immunoreceptors resides in their association at the cell surface with transmembrane signaling adaptors. Several adaptors, such as the CD3 molecules, FcRγ and KARAP/DAP12, harbor intracytoplasmic immunoreceptor tyrosine-based activation motifs (ITAM) that activate Syk-family protein tyrosine kinases. In contrast, another transmembrane adaptor, DAP10, bears a YxxM motif that delivers signals by activation of lipid kinase pathways. We show here that the human signal-regulatory protein SIRPβ1 can associate with both DAP10 and KARAP/DAP12 in a model of RBL-2H3 cell transfectants. In association with KARAP/DAP12, SIRPβ1 complexes are capable of inducing serotonin release and tumor necrosis factor (TNF) secretion. By contrast,in the absence of KARAP/DAP12, engagement of SIRPβ1:DAP10 complexes does not lead to detectable serotonin release or TNF secretion by RBL-2H3 transfectants. However, triggering of SIRPβ1:DAP10 complexes co-stimulates RBL-2H3 effector function induced by sub-optimal stimulation of the endogenous FcϵRI complex. Therefore, we report here a cellular model in which the association of a cell surface receptor with various signaling adaptors dictates the co-stimulatory or the direct stimulatory properties of the complex.
- Publication
European Journal of Immunology, 2003, Vol 33, Issue 12, p3514
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.200324573