Title : N-linked glycosylations at
Asn(26) and Asn(114) of human
MD-2 are required for
toll-like receptor 4-mediated activation of NF-kappaB by lipopolysaccharide
Abstract :
- 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 ( Asn(26) and Asn(114) ) 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 Asn(26) and Asn(114)
- 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-kappaB 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 Asn(26) and Asn(114) , and that these glycosylations are crucial for TLR4-mediated signal transduction of LPS
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. glycosylations, , -, -, Asn(26) and Asn(114)
- 0. glycosylations, , MD-2, -, Asn(26) and Asn(114)
- 4. glycosylation, , -, -, Asn(26) and Asn(114)
- 4. glycosylation, , MD-2, -, Asn(26) and Asn(114)
- 4. glycosylation, , MD-2, -, sites
- 4. sites, , -, -, Asn(26) and Asn(114)
- 4. sites, , -, -, sites
- 7. glycosylation, , -, -, Asn(26) and Asn(114)
- 7. glycosylation, , hMD-2, -, Asn(26) and Asn(114)
Output(Part-Of) (sent_index,
protein,
site):
- 4. MD-2, Asn(26) and Asn(114)
- 4. MD-2, sites
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):
- 0. MD-2, -, Asn(26) and Asn(114)
- 4. MD-2, -, Asn(26) and Asn(114)
- 7. hMD-2, -, Asn(26) and Asn(114)