title: Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells.
abstract: We have analyzed leukocyte mono-Ig-like receptor 5 (LMIR5) as an activating receptor among paired LMIRs. Mouse LMIR5 (mLMIR5) is expressed in myeloid cells such as mast cells, granulocytes, macrophages, and dendritic cells. Cross-linking of transduced mLMIR5 in bone marrow-derived mast cells (BMMCs) caused activation events, including cytokine production, cell survival, degranulation, and adhesion to the extracellular matrix. mLMIR5 associated with DAP12 and to a lesser extent with DAP10, and mLMIR5-mediated functions of BMMCs were strongly inhibited by DAP12 deficiency. Importantly, cross-linking of endogenous mLMIR5 induced Syk-dependent activation of fetal liver-derived mast cells. Unlike mLMIR5, cross-linking of human LMIR5 (hLMIR5) induced cytokine production of BMMCs even in the absence of both DAP12 and DAP10, suggesting the existence of unidentified adaptors. Interestingly, hLMIR5 possessed a tyrosine residue (Y188) in the cytoplasmic region. Signaling via Y188 phosphorylation played a predominant role in hLMIR5-mediated cytokine production in DAP12-deficient, but not wild-type BMMCs. In addition, experiments using DAP10/DAP12 double-deficient BMMCs suggested the existence of Y188 phoshorylation-dependent and -independent signals from unidentified adaptors. Collectively, although both mouse and human LMIR5 play activatory roles in innate immunity cells, the functions of LMIR5 were differentially regulated in mouse versus human cells.
authors.affiliation: Institute of Medical Science, University of Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamanishi
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
authors.forename: Kumi
authors.initials: K
authors.lastname: Izawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsuoka
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Oki
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Fumi
authors.initials: F
authors.lastname: Shibata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Kumagai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Mari
authors.initials: M
authors.lastname: Maeda-Yamamoto
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takai
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007152:Immunologic Capping / Q000502:physiology; D007962:Leukocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; C120528:HCST protein, human; C492355:Hcst protein, mouse; C527073:LMIR5 protein, mouse; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human; C484963:Tyrobp protein, mouse