title: IREM-1 is a novel inhibitory receptor expressed by myeloid cells.
abstract: Using a three-hybrid strategy, we have identified a novel cell surface molecule which interacts with the Src homology 2 (SH2) domains of SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1), termed "immune receptor expressed on myeloid cells 1" (IREM-1). The full-length cDNA coding for a polypeptide of 290 amino acids presents an extracellular single V-type Ig domain, a transmembrane region and a cytoplasmic tail with five tyrosine residues, two of which are in the context of an immunoreceptor tyrosine-based inhibitory motif. Moreover, cDNA encoding for three other splicing forms of IREM-1, named IREM-1 splice variant (Sv)1, Sv2 and Sv3 were cloned by reverse transcription (RT)-PCR. The gene encoding for IREM-1 contains nine exons, is located on human chromosome 17 (17q25.1) and is homologous to previously identified molecules termed CMRF-35 and IRp60. RT-PCR, northern blot and FACS analysis with specific monoclonal antibodies indicated that IREM-1 is expressed on monocytes, granulocytes, and myeloid leukemia cell lines. Western blot analysis confirmed the recruitment of SHP-1 to IREM-1 and demonstrated that phosphotyrosine residue 205 is the main docking site for this interaction. Finally, cross-linking of IREM-1 results in the inhibition of FcRepsilon-induced activation. Our results indicate that IREM-1 is a novel inhibitory receptor of the Ig superfamily in myeloid cells.
authors.affiliation: Molecular Immunopathology Unit, DCEXS, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Damiana
authors.initials: D
authors.lastname: Alvarez-Errico
authors.forename: Helena
authors.initials: H
authors.lastname: Aguilar
authors.forename: Friederike
authors.initials: F
authors.lastname: Kitzig
authors.forename: Tamara
authors.initials: T
authors.lastname: Brckalo
authors.forename: Joan
authors.initials: J
authors.lastname: Sayós
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D000595:Amino Acid Sequence; D000954:Antigens, Surface; D001483:Base Sequence; D003001:Cloning, Molecular; D015536:Down-Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D022423:Myeloid Cells / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; C444139:CD300C protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D014443:Tyrosine; D054645:Protein Phosphatase 1; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases