title: Identification and characterization of S2V, a novel putative siglec that contains two V set Ig-like domains and recruits protein-tyrosine phosphatases SHPs.
abstract: We describe the molecular cloning and characterization of S2V, a novel sialic acid binding immunoglobulin-like lectin. The cDNA of S2V encodes a type 1 transmembrane protein with four extracellular immunoglobulin-like (Ig-like) domains and a cytoplasmic tail bearing a typical immunoreceptor tyrosine-based inhibitory motif (ITIM) and an ITIM-like motif. A unique feature of S2V is the presence of two V-set Ig-like domains responsible for the binding to sialic acid, whereas all other known siglecs possess only one. S2V is predominantly expressed in macrophage. In vivo S2V was tyrosine-phosphorylated when co-expressed with exogenous c-Src kinase. Upon tyrosine phosphorylation, S2V recruits both Src homology 2 (SH2) domain-containing protein-tyrosine phosphatases SHP-1 and SHP-2, two important inhibitory regulators of immunoreceptor signal transduction. These findings suggest that S2V is involved in the negative regulation of the signaling in macrophage by functioning as an inhibitory receptor. When expressed in COS-7 cells, S2V was able to mediate sialic acid-dependent binding to human red blood cells, suggesting that S2V may function through cell-cell interaction.
authors.affiliation: Pharmaceutical Sector, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.forename: C M
authors.initials: CM
authors.lastname: Lai
authors.forename: M
authors.initials: M
authors.lastname: Maoui
authors.forename: D
authors.initials: D
authors.lastname: Banville
authors.forename: S H
authors.initials: SH
authors.lastname: Shen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D017386:Sequence Homology, Amino Acid
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C402206:SIGLEC7 protein, human; C076414:SV2A protein, human; D016392:Proto-Oncogene Proteins pp60(c-src); C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D019158:N-Acetylneuraminic Acid