Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells.
We have identified and characterized two mouse cDNAs in a mouse antigen-stimulated bone marrow-derived mast cell cDNA library, both of which encode type I transmembrane proteins. The genes were closely mapped in the distal region of mouse chromosome 11 and expressed not only in mast cells but also widely in leukocytes. The extracellular domains of their encoded proteins contain a single variable immunoglobulin (Ig) motif sharing about 90% identity with amino acids, showing that they comprise a pair of molecules and belong to the Ig superfamily. We named these molecules leukocyte mono-Ig-like receptor1 and 2 (LMIR1 and 2). The intracellular domain of LMIR1 contains several immunoreceptor tyrosine-based inhibition motifs (ITIMs). When cross-linked, the intracellular domain was tyrosine phosphorylated and capable of recruiting tyrosine phosphatases, SHP-1 and SHP-2 and inositol polyphosphate 5-phosphatase, SHIP. LMIR2, on the other hand, contains a short cytoplasmic tail and a characteristic transmembrane domain carrying two positively charged amino acids associated with three kinds of immunoreceptor tyrosine-based activation motif (ITAM)-bearing molecules, DAP10, DAP12, and FcRgamma. These findings suggest that a new pair of ITIM/ITAM-bearing receptors, LMIR1 and 2, regulate mast cell-mediated inflammatory responses through yet to be defined ligand(s).
Kumagai
Hidetoshi
H
Division of Hematopoietic Factors, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 6-1 Shirokanedai-4-chome, Minato-ku, Tokyo 108-8639, Japan.
Oki
Toshihiko
T
Tamitsu
Kaori
K
Feng
Si Zhou
SZ
Ono
Masao
M
Nakajima
Hideaki
H
Bao
Ying Chun
YC
Kawakami
Yuko
Y
Nagayoshi
Kazunari
K
Copeland
Neal G
NG
Gilbert
Debra J
DJ
Jenkins
Nancy A
NA
Kawakami
Toshiaki
T
Kitamura
Toshio
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006412:Hematopoietic Stem Cells / Q000502:physiology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D017434:Protein Structure, Tertiary; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
C476771:LMIR1 protein, mouse; C476772:LMIR2 protein, mouse; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D014443:Tyrosine; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; C098706:INPPL1 protein, human; D000072183:Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases