NKG2-D type II integral membrane protein

Definition:

Functions as an activating and costimulatory receptor involved in immunosurveillance upon binding to various cellular stress-inducible ligands displayed at the surface of autologous tumor cells and virus-infected cells. Provides both stimulatory and costimulatory innate immune responses on activated killer (NK) cells, leading to cytotoxic activity. Acts as a costimulatory receptor for T-cell receptor (TCR) in CD8(+) T-cell-mediated adaptive immune responses by amplifying T-cell activation. Stimulates perforin-mediated elimination of ligand-expressing tumor cells. Signaling involves calcium influx, culminating in the expression of TNF-alpha. Participates in NK cell-mediated bone marrow graft rejection. May play a regulatory role in differentiation and survival of NK cells. Binds to ligands belonging to various subfamilies of MHC class I-related glycoproteins including MICA, MICB, RAET1E, RAET1G, RAET1L/ULBP6, ULBP1, ULBP2, ULBP3 (ULBP2>ULBP1>ULBP3) and ULBP4.

References:

[1]. Robert A Eagle, et al. ULBP6/RAET1L is an additional human NKG2D ligand. Eur J Immunol. 2009 Nov;39(11):3207-16. [Content Brief]

[2]. David H Raulet, et al. Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol. 2013;31:413-41. [Content Brief]

[3]. J Wu, et al. An activating immunoreceptor complex formed by NKG2D and DAP10. Science. 1999 Jul 30;285(5428):730-2. [Content Brief]

[4]. Louise Bacon, et al. Two human ULBP/RAET1 molecules with transmembrane regions are ligands for NKG2D. J Immunol. 2004 Jul 15;173(2):1078-84. [Content Brief]

[5]. Biljana Zafirova, et al. Regulation of immune cell function and differentiation by the NKG2D receptor. Cell Mol Life Sci. 2011 Nov;68(21):3519-29. [Content Brief]

[6]. V Groh, et al. Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol. 2001 Mar;2(3):255-60. [Content Brief]

[7]. Jianmin Zuo, et al. A disease-linked ULBP6 polymorphism inhibits NKG2D-mediated target cell killing by enhancing the stability of NKG2D ligand binding. Sci Signal. 2017 May 30;10(481):eaai8904. [Content Brief]

[8]. Claire L Sutherland, et al. UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol. 2002 Jan 15;168(2):671-9. [Content Brief]

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