3rp1

Structural highlights

Function

[LAIR1_HUMAN] Functions as an inhibitory receptor that plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. May also play its inhibitory role independently of SH2-containing phosphatases. Modulates cytokine production in CD4+ T-cells, down-regulating IL2 and IFNG production while inducing secretion of transforming growth factor beta. Down-regulates also IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. Inhibits proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells. Inhibits the differentiation of peripheral blood precursors towards dendritic cells.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Meyaard L, Adema GJ, Chang C, Woollatt E, Sutherland GR, Lanier LL, Phillips JH. LAIR-1, a novel inhibitory receptor expressed on human mononuclear leukocytes. Immunity. 1997 Aug;7(2):283-90. PMID:9285412
2. ↑ Meyaard L, Hurenkamp J, Clevers H, Lanier LL, Phillips JH. Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells. J Immunol. 1999 May 15;162(10):5800-4. PMID:10229813
3. ↑ Xu M, Zhao R, Zhao ZJ. Identification and characterization of leukocyte-associated Ig-like receptor-1 as a major anchor protein of tyrosine phosphatase SHP-1 in hematopoietic cells. J Biol Chem. 2000 Jun 9;275(23):17440-6. PMID:10764762 doi:10.1074/jbc.M001313200
4. ↑ Poggi A, Tomasello E, Ferrero E, Zocchi MR, Moretta L. p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor. Eur J Immunol. 1998 Jul;28(7):2086-91. PMID:9692876 doi:10.1002/(SICI)1521-4141(199807)28:07<2086::AID-IMMU2086>3.0.CO;2-T
5. ↑ Poggi A, Pellegatta F, Leone BE, Moretta L, Zocchi MR. Engagement of the leukocyte-associated Ig-like receptor-1 induces programmed cell death and prevents NF-kappaB nuclear translocation in human myeloid leukemias. Eur J Immunol. 2000 Oct;30(10):2751-8. PMID:11069054
6. ↑ Sathish JG, Johnson KG, Fuller KJ, LeRoy FG, Meyaard L, Sims MJ, Matthews RJ. Constitutive association of SHP-1 with leukocyte-associated Ig-like receptor-1 in human T cells. J Immunol. 2001 Feb 1;166(3):1763-70. PMID:11160222
7. ↑ Saverino D, Fabbi M, Merlo A, Ravera G, Grossi CE, Ciccone E. Surface density expression of the leukocyte-associated Ig-like receptor-1 is directly related to inhibition of human T-cell functions. Hum Immunol. 2002 Jul;63(7):534-46. PMID:12072189
8. ↑ Merlo A, Tenca C, Fais F, Battini L, Ciccone E, Grossi CE, Saverino D. Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and cytokine production by human B lymphocytes. Clin Diagn Lab Immunol. 2005 Jun;12(6):705-12. PMID:15939744 doi:12/6/705
9. ↑ Maasho K, Masilamani M, Valas R, Basu S, Coligan JE, Borrego F. The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at high levels by human naive T cells and inhibits TCR mediated activation. Mol Immunol. 2005 Aug;42(12):1521-30. Epub 2005 Feb 24. PMID:15950745 doi:10.1016/j.molimm.2005.01.004
10. ↑ Verbrugge A, Rijkers ES, de Ruiter T, Meyaard L. Leukocyte-associated Ig-like receptor-1 has SH2 domain-containing phosphatase-independent function and recruits C-terminal Src kinase. Eur J Immunol. 2006 Jan;36(1):190-8. PMID:16380958 doi:10.1002/eji.200535226