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Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
In this study, we describe the characterization of human CD300b, a novel member of the CMRF-35/immune receptor expressed by myeloid cell (IREM) multigene family of immune receptors. Immune receptor expressed by myeloid cell-3 cDNA was cloned from a PHA-activated PBMC library and RT-PCR revealed the gene to be expressed preferentially in cells of myeloid origin. The CD300b cDNA open reading frame encodes a 201-aa type I protein composed of a single extracellular Ig V-type domain followed by a transmembrane region containing a positively charged residue (lysine) which is a common feature among receptors that associate with activating adaptor proteins. Indeed, CD300b was able to associate with DNAX-activating protein of 12 kDa (DAP-12) and deliver different activating signals through this ITAM-based adaptor. Unusually for an activating receptor, the 29-aa cytoplasmic tail of CD300b contains a tyrosine-based motif that, upon c-Fyn phosphorylation, became a docking site for the intracellular signaling mediator growth factor receptor-bound protein 2. Moreover, in the absence of DAP-12, CD300b was able to activate NFAT/AP-1-dependent transcriptional activity in RBL-2H3 cells. This activity could be abolished only by mutating both the cytoplasmic tyrosine and the transmembrane lysine. Our data suggest the existence of an unidentified molecule capable of interacting with CD300b through a charged residue of the transmembrane region and allowing receptor signaling independent of DAP-12. Therefore, CD300b defines a nonclassical Ig receptor able to trigger signals by coupling distinct mediators and thus initiating different signaling pathways.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from Plan Nacional de I+D (SAF2004-00972). A.M.-B. was supported by a fellowship from the Ministerio de Ciencia y Tecnología, and J.S. was supported by a contract Ramon y Cajal from Ministerio de Ciencia y Tecnología.
2 Address correspondence and reprint requests to Dr. Joan Sayós, Molecular Immunopathology Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Doctor Aiguader 80, 08003 Barcelona, Spain. E-mail address: joan.sayos{at}upf.edu
3 Abbreviations used in this paper: SH2, Src homology 2; Grb2, growth factor receptor-bound protein 2; HA, hemagglutinin; WT, wild type; mIREM, murine IREM; Tx-100, Triton X-100; TREM, triggering receptor expressed on myeloid cell; SH3, Src homology 3; SHP-1, SH2 domain-containing phosphatase 1; PVDF, polyvinylidene difluoride; DAP-12, DNAX-activating protein of 12 kDa; KARAP, killer cell-activating receptor-associated protein; IREM, immune receptor expressed by myeloid cell.
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