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- W2743167593 abstract "Natural killer (NK) cells represent the first lymphoid subpopulation in the defense against tumors and viral infection. The activity of NK cells is regulated by the interplay of activating and inhibitory surface receptors. The mechanisms by which these receptors transduce their signals and the integration of positive and negative signals are not completely understood. 2B4 (CD244) is an important activating NK cell receptor. Ligand engagement results in the recruitment of 2B4 to membrane microdomains, which is essential for the function of this receptor. Here we successfully established a new approach to investigate membrane microdomains without destroying the membrane’s natural composition, as it has often been criticized for the classical cold non-ionic detergent lysis followed by sucrose density gradient centrifugation. NK cell receptors were stimulated by antibodies coupled to magnetic beads. NK cells were then physically disrupted in a nitrogen-cavitation bomb and membrane fragments surrounding the engaged receptor including the associated signaling machinery were immunoisolated by separation of the magnetic beads. By comparing bead contents of activating (2B4) with inhibitory (NKG2A) NK cell receptors using 2D-DIGE, several proteins with significant difference emerged, which were subsequently identified by mass spectrometry. Important candidates for cytoskeletal remodeling and signal transduction were identified to be specifically associated with 2B4, which gave us a first hint for the formation of multimolecular complexes and their role in the early steps of NK cell activation. In a second project we analyzed the glycosylation of 2B4. We demonstrated that 2B4 is heavily and differentially glycosylated in primary human NK cells and NK cell lines. The differential glycosylation of 2B4 could be attributed to sialic acid residues on N- and O-linked carbohydrates. Glycosylation plays an important role in receptor-ligand recognition and interaction but may also lead to repulsion between molecules. Using a recombinant fusion protein of the extracellular domain of 2B4 we demonstrated that N-linked glycosylation of 2B4 is essential for binding to its ligand CD48. In contrast, sialylation of 2B4 had a negative impact on ligand binding as the interaction between 2B4 and CD48 was increased after the removal of sialic acids. This was confirmed in a functional assay system, where the desialylation of NK cells or the inhibition of O-linked glycosylation resulted in increased 2B4-mediated lysis of CD48 expressing tumor target cells. These data demonstrate that glycosylation has an important impact on 2B4-mediated NK cell function and suggest that regulated changes in glycosylation during NK cell development and activation might be involved in the regulation of NK cell responses." @default.
- W2743167593 created "2017-08-17" @default.
- W2743167593 creator A5063591082 @default.
- W2743167593 date "2010-01-01" @default.
- W2743167593 modified "2023-09-28" @default.
- W2743167593 title "Membrane microdomains and glycosylation of activating receptors influence natural killer cell regulation" @default.
- W2743167593 cites W1492762298 @default.
- W2743167593 cites W1493250995 @default.
- W2743167593 cites W1507560413 @default.
- W2743167593 cites W1512205565 @default.
- W2743167593 cites W1528512758 @default.
- W2743167593 cites W1564861448 @default.
- W2743167593 cites W1573739626 @default.
- W2743167593 cites W1574178834 @default.
- W2743167593 cites W1582703272 @default.
- W2743167593 cites W1662706554 @default.
- W2743167593 cites W1670186976 @default.
- W2743167593 cites W1823215648 @default.
- W2743167593 cites W1845375977 @default.
- W2743167593 cites W1857381704 @default.
- W2743167593 cites W1905151522 @default.
- W2743167593 cites W1963309870 @default.
- W2743167593 cites W1964415050 @default.
- W2743167593 cites W1966137027 @default.
- W2743167593 cites W1966938433 @default.
- W2743167593 cites W1969415487 @default.
- W2743167593 cites W1969950463 @default.
- W2743167593 cites W1972529519 @default.
- W2743167593 cites W1974373686 @default.
- W2743167593 cites W1975149550 @default.
- W2743167593 cites W1975317988 @default.
- W2743167593 cites W1975325447 @default.
- W2743167593 cites W1978147073 @default.
- W2743167593 cites W1978281474 @default.
- W2743167593 cites W1978579655 @default.
- W2743167593 cites W1981916955 @default.
- W2743167593 cites W1988441535 @default.
- W2743167593 cites W1988927480 @default.
- W2743167593 cites W1991218269 @default.
- W2743167593 cites W1992557186 @default.
- W2743167593 cites W1994047471 @default.
- W2743167593 cites W1994251377 @default.
- W2743167593 cites W1994347380 @default.
- W2743167593 cites W1995030412 @default.
- W2743167593 cites W1995875818 @default.
- W2743167593 cites W1996141054 @default.
- W2743167593 cites W1996787721 @default.
- W2743167593 cites W1996891899 @default.
- W2743167593 cites W2000638372 @default.
- W2743167593 cites W2000772846 @default.
- W2743167593 cites W2001311508 @default.
- W2743167593 cites W2002051002 @default.
- W2743167593 cites W2004296371 @default.
- W2743167593 cites W2005765588 @default.
- W2743167593 cites W2006711580 @default.
- W2743167593 cites W2007767964 @default.
- W2743167593 cites W2008299431 @default.
- W2743167593 cites W2008338411 @default.
- W2743167593 cites W2012522079 @default.
- W2743167593 cites W2014472703 @default.
- W2743167593 cites W2014987538 @default.
- W2743167593 cites W2016329950 @default.
- W2743167593 cites W2018196736 @default.
- W2743167593 cites W2020686415 @default.
- W2743167593 cites W2021211941 @default.
- W2743167593 cites W2021750684 @default.
- W2743167593 cites W2022754675 @default.
- W2743167593 cites W2023858678 @default.
- W2743167593 cites W2024191848 @default.
- W2743167593 cites W2024579897 @default.
- W2743167593 cites W2029175463 @default.
- W2743167593 cites W2030546554 @default.
- W2743167593 cites W2030743328 @default.
- W2743167593 cites W2033107431 @default.
- W2743167593 cites W2035041737 @default.
- W2743167593 cites W2035699435 @default.
- W2743167593 cites W2036166762 @default.
- W2743167593 cites W2036458764 @default.
- W2743167593 cites W2040079201 @default.
- W2743167593 cites W2042113030 @default.
- W2743167593 cites W2042202484 @default.
- W2743167593 cites W2043305034 @default.
- W2743167593 cites W2045868744 @default.
- W2743167593 cites W2050153157 @default.
- W2743167593 cites W2050343039 @default.
- W2743167593 cites W2054150065 @default.
- W2743167593 cites W2054218102 @default.
- W2743167593 cites W2056771287 @default.
- W2743167593 cites W2056918775 @default.
- W2743167593 cites W2061229343 @default.
- W2743167593 cites W2061372590 @default.
- W2743167593 cites W2063015454 @default.
- W2743167593 cites W2064789528 @default.
- W2743167593 cites W2067759988 @default.
- W2743167593 cites W2069945609 @default.
- W2743167593 cites W2072584472 @default.
- W2743167593 cites W2075271989 @default.
- W2743167593 cites W2076118339 @default.
- W2743167593 cites W2076248543 @default.
- W2743167593 cites W2076329388 @default.