Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Biochim Biophys Acta ; 1793(10): 1579-87, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19654028

ABSTRACT

Death receptor 6 (DR6/TNFRSF21) is a death domain-containing receptor of the TNFR superfamily with an apparent regulatory function in hematopoietic and neuronal cells. In this study we document that DR6 is an extensively posttranslationally modified transmembrane protein and that N- and O-glycosylations of amino acids in its extracellular part are mainly responsible for its approximately 40 kDa mobility shift in SDS polyacrylamide gels. Site-directed mutagenesis confirmed that all six extracellular asparagines are N-glycosylated and that the Ser/Thr/Pro cluster in the "stalk" domain juxtaposed to the cysteine-rich domains (CRDs) is a major site for the likely mucine-type of O-glycosylation. Deletion of the entire linker region between CRDs and the transmembrane domain, spanning over 130 amino acids, severely compromises the plasma membrane localization of DR6 and leads to its intracellular retention. Biosynthetic labeling with radiolabeled palmitate and side-directed mutagenesis also revealed that the membrane-proximal Cys368 in the intracellular part of DR6 is, similarly as cysteines in Fas/CD95 or DR4 ICPs, S-palmitoylated. However, palmitoylation of Cys368 is apparently not required for DR6 targeting into Brij-98 insoluble lipid rafts. In contrast, we show that N-glycosylation of the extracellular part might participate in directing DR6 into these membrane microdomains.


Subject(s)
Receptors, Tumor Necrosis Factor/chemistry , Receptors, Tumor Necrosis Factor/metabolism , Cell Line , Cell Line, Tumor , Glycosylation , HL-60 Cells , HeLa Cells , Humans , Jurkat Cells , Lipoylation , Male , Membrane Microdomains/metabolism , Molecular Weight , Mutagenesis, Site-Directed , Protein Isoforms/chemistry , Protein Isoforms/genetics , Protein Isoforms/physiology , Protein Processing, Post-Translational , Protein Structure, Tertiary , Receptors, Tumor Necrosis Factor/genetics , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sequence Deletion
SELECTION OF CITATIONS
SEARCH DETAIL
...