C5: Fucosyltransferase IX vermittelte Synthese der Lewisx-Gruppen von CEACAM1: Bedeutung für die Interaktion mit DC-SIGN und dendritischen Zellen
CEACAM1 (carcinoembryonic antigen (CEA)-related cell adhesion molecule 1) is an adhesion molecule of the immunoglobulin superfamily. We assume that sLex glycans on CEACAM1 participate in CEACAM1-mediated angiogenesis through binding to E-selectin. Considering homophilic trans-interactions, Lex glycans might be subtle fine-tuning regulators of CEACAM1-CEACAM1 binding on adjacent cells. The specific decoration of CEACAM1 with Lex glycans suggests that CEACAM1 exhibits unique structural features for a fucosylation through cognate fucosyltransferases. These hypotheses will be investigated by co-transfection experiments of CEACAM1 and different fucosyltransferases in order to generate Lex and sLex glycans on CEACAM1 selectively. By using transfected cells and purified CEACAM1, we will analyse the biological role of Lewis glycans in CEACAM1-mediated angiogenesis as well as the CEACAM1-CEACAM1 homophilic binding. Furthermore, we the specific structural requirements for selective expression of Lex glycans on CEACAM1 will be analysed by site-directed mutagenesis.
In collaboration with Prof. Dr. W. Reutter's laboratory at the FU Berlin (Drs. Christoph Kannicht and Lothar Lucka), we have analysed the sugar moieties on native and recombinant CEACAM1 and could confirm the presence of Lex glycans on native CEACAM1 (source: human granulocytes). Lex glycans are not expressed on recombinant CEACAM1 obtained after single transfection of HEK293 cells, as confirmed by mass spectrometry.
Contact:
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Prof. Dr. Christoph Wagener / PD Dr. Peter Nollau Address: Institut für Klinische Chemie Universitätsklinikum Hamburg-Eppendorf Martinistr. 52 20251 Hamburg Telefon: 040-42803-2981 (CW) Telefon: 040-42803-2950 (PN) Telefax: 040-42803-4621 (CW) Telefax: 040-42803-4971 (PN) E-Mail: wagener@uke.uni-hamburg.de; nollau@uke.uni-hamburg.de http://www.uke.uni-hamburg.de/institute/klinische-chemie/index.php |
Prof. Dr. Christoph Wagener |