The mouse homologue of the leukocyte-associated Ig-like receptor-1 is an inhibitory receptor that recruits Src homology region 2-containing protein tyrosine phosphatase (SHP)-2, but not SHP-1.
We report the molecular cloning and characterization of the first leukocyte-associated Ig-like receptor 1 (LAIR-1) homologue in mice that we have named mouse LAIR-1 (mLAIR-1). The mLAIR-1 gene maps to the proximal end of mouse chromosome 7 in a region syntenic with human chromosome 19q13.4 where the leukocyte receptor cluster is located. The protein shares 40% sequence identity with human LAIR-1, has a single Ig-like domain, and contains two immunoreceptor tyrosine-based inhibitory motif-like structures in its cytoplasmic tail. Mouse LAIR-1 is broadly expressed on various immune cells, and cross-linking of the molecule on stably transfected RBL-2H3 and YT.2C2 cells results in strong inhibition of their degranulation and cytotoxic activities, respectively. Upon pervanadate stimulation, the mLAIR-1 cytoplasmic tail becomes phosphorylated, thereby recruiting Src homology region 2-containing tyrosine phosphatase-2. Interestingly, unlike human LAIR-1, Src homology region 2-containing tyrosine phosphatase-1 is not recruited to the mLAIR-1 cytoplasmic tail. Screening human and mouse cell lines for mLAIR-1 and human LAIR-1 binding partners identified several lines expressing putative ligand(s) for both receptors.
Lebbink
Robert Jan
RJ
Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
de Ruiter
Talitha
T
Verbrugge
Annelies
A
Bril
Wendy S
WS
Meyaard
Linde
L
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology*; D019073:HT29 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D011485:Protein Binding; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D026801:Synteny; D014638:Vanadates / Q000494:pharmacology; D018909:src Homology Domains / Q000276:immunology
D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1; C076715:pervanadate; D014638:Vanadates; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases