RT Journal Article
T1 Differential Mechanisms of Shedding of the Glycosylphosphatidylinositol (GPI)-anchored NKG2D Ligands
A1 Fernández Messina, Lola María
A1 Ashiru, Omodele
A1 Boutet, Philippe
A1 Agüera-González, Sonia
A1 Skepper, Jeremy
A1 Reyburn, Hugh
A1 Valés-Gómez, Mar
AB Tumor cells release NKG2D ligands to evade NKG2D-mediated immune surveillance. The purpose of our investigation was to explore the cellular mechanisms of release used by various members of the ULBP family. Using biochemical and cellular approaches in both transfectant systems and tumor cell lines, this paper shows that ULBP1, ULBP2, and ULBP3 are released from cells with different kinetics and by distinct mechanisms. Whereas ULBP2 is mainly shed by metalloproteases, ULBP3 is abundantly released as part of membrane vesicles known as exosomes. Interestingly, exosomal ULBP3 protein is much more potent for down-modulation of the NKG2D receptor than soluble ULBP2 protein. This is the first report showing functionally relevant differences in the biochemistry of the three members of the ULBP family and confirms that in depth study of the biochemical features of individual NKG2D ligands will be necessary to understand and manipulate the biology of these proteins for therapy.
PB Elsevier
SN 0021-9258
YR 2010
FD 2010
LK https://hdl.handle.net/20.500.14352/97218
UL https://hdl.handle.net/20.500.14352/97218
LA eng
NO Fernández-Messina, Lola, et al. «Differential Mechanisms of Shedding of the Glycosylphosphatidylinositol (GPI)-Anchored NKG2D Ligands». Journal of Biological Chemistry, vol. 285, n.o 12, marzo de 2010, pp. 8543-51. https://doi.org/10.1074/jbc.M109.045906.
NO AcknowledgmentsWe thank R. Apps for the ULBP constructs; N. Miller for assistance with cell sorting and F. Colucci and his group, M. Field, J. Kaufman, A. Kelly, S. Powis, P. Roda-Navarro and J. Trowsdale for helpful discussions.
DS Docta Complutense
RD 21 dic 2025