RT Journal Article
T1 The human NKG2D ligand ULBP2 can be expressed at the cell surface with or without a GPI anchor and both forms can activate NK cells
A1 Fernández Messina, Lola María
A1 Ashiru, Omodele
A1 Agüera-González, Sonia
A1 Reyburn, Hugh
A1 Valés-Gómez, Mar
AB The activating immune receptor NKG2D binds to several stress-induced ligands that are structurally different. MHC-class-I-related chain (MIC) A/B molecules have a transmembrane domain, whereas most UL16 binding proteins (ULBPs) are glycosylphosphatidylinositol (GPI)-linked molecules. The significance of this variability in membrane anchors is unclear. Here, we demonstrate that ULBP2, but not ULBP1 or ULBP3, can reach the cell surface without the GPI modification. Several proteins are expressed at the cell surface as both transmembrane and GPI-linked molecules, either via alternative splicing or by the expression of linked genes. However, to our knowledge, ULBP2 is the first single mammalian cDNA that can be expressed as either a transmembrane or a GPI-anchored protein. The rate of maturation and the levels of cell surface expression of the non-GPI-linked form were lower than those of the GPI-linked ULBP2. Nonetheless, non-GPI ULBP2 was recognised by NKG2D and triggered NK cell cytotoxicity. These data show that differences in membrane attachment by NKG2D ligands are more important for regulation of their surface expression than for cytotoxic recognition by NKG2D and emphasise that detailed characterisation of the cell biology of individual NKG2D ligands will be necessary to allow targeted modulation of this system.
PB The Company of Biologists
SN 0021-9533
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/97257
UL https://hdl.handle.net/20.500.14352/97257
LA eng
NO Lola Fernández-Messina, Omodele Ashiru, Sonia Agüera-González, Hugh T. Reyburn, Mar Valés-Gómez; The human NKG2D ligand ULBP2 can be expressed at the cell surface with or without a GPI anchor and both forms can activate NK cells. J Cell Sci 1 February 2011; 124 (3): 321–327. doi: https://doi.org/10.1242/jcs.076042
NO AcknowledgementsThe authors would like to thank Drs M. E. Medof, V. L. Stevens and S. Vainauskas for GPI-deficient cell lines; C. Gross and F. Colucci for critically reading the manuscript. This work was supported by the MRC (New Investigator Grant to M.V.-G.) and FIS (PS09/00181 and PI08/1701). O.A. was supported by the Leukaemia Research Fund and The Newton Trust. S.A.-G. was supported by Fundación Caja Madrid and Ibercaja. Deposited in PMC for release after 6 months.
NO Leukaemia Research Fund
NO The Isaac Newton Trust
NO Fundación Caja Madrid
NO Ibercaja
NO Medical Research Council (UK)
DS Docta Complutense
RD 7 abr 2025