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B by Lipopolysaccharide
Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan
MD-2 is physically associated with Toll-like receptor 4 (TLR4) and
is required for TLR4-mediated LPS signaling. Western blotting analysis
revealed the presence of three forms of human (h)MD-2 with different
electrophoretic mobilities. After N-glycosidase
treatment of the cellular extract prepared from cells expressing hMD-2,
only a single form with the fastest mobility was detected. Mutation of
either one of two potential glycosylation sites (Asn26 and
Asn114) of MD-2 resulted in the disappearance of the
slowest mobility form, and only the fastest form was detected in hMD-2
carrying mutations at both Asn26 and Asn114.
Although these mutants were expressed on the cell surface and
maintained its ability to associate with human TLR4, these mutations or
tunicamycin treatment substantially impaired the ability of MD-2 to
complement TLR4-mediated activation of NF-
B by LPS. LPS binding to
cells expressing CD14, TLR4, and MD-2 was unaffected by these
mutations. These observations demonstrate that hMD-2 undergoes
N-linked glycosylation at Asn26 and
Asn114, and that these glycosylations are crucial for
TLR4-mediated signal transduction of LPS.
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