title: Contrasting roles of DAP10 and KARAP/DAP12 signaling adaptors in activation of the RBL-2H3 leukemic mast cell line.
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, FcRgamma 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 SIRPbeta1 can associate with both DAP10 and KARAP/DAP12 in a model of RBL-2H3 cell transfectants. In association with KARAP/DAP12, SIRPbeta1 complexes are capable of inducing serotonin release and tumor necrosis factor (TNF) secretion. By contrast,in the absence of KARAP/DAP12, engagement of SIRPbeta1:DAP10 complexes does not lead to detectable serotonin release or TNF secretion by RBL-2H3 transfectants. However, triggering of SIRPbeta1:DAP10 complexes co-stimulates RBL-2H3 effector function induced by sub-optimal stimulation of the endogenous FcepsilonRI 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.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Anfossi
authors.forename: Mathias
authors.initials: M
authors.lastname: Lucas
authors.forename: Andreas
authors.initials: A
authors.lastname: Diefenbach
authors.forename: Hans-Jörg
authors.initials: HJ
authors.lastname: Bühring
authors.forename: David
authors.initials: D
authors.lastname: Raulet
authors.forename: Elena
authors.initials: E
authors.lastname: Tomasello
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation; D045744:Cell Line, Tumor; D019281:Dimerization; D006801:Humans; D008407:Mast Cells / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology*; D054340:Receptors, KIR; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; C120528:HCST protein, human; C433932:KIR2DS2 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039842:Neural Cell Adhesion Molecule L1; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D054340:Receptors, KIR; C501921:SIRPB1 protein, human; C110546:TYROBP protein, human; C054979:antigen T cell receptor, zeta chain