Glycosylation regulates turnover of cyclooxygenase-2.
Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in the prostanoid biosynthesis pathway, converting arachidonic acid into prostaglandin H(2). COX-2 exists as 72 and 74kDa glycoforms, the latter resulting from an additional oligosaccharide chain at residue Asn(580). In this study, Asn(580) was mutated to determine the biological significance of this variable glycosylation. COS-1 cells transfected with the mutant gene were unable to express the 74kDa glycoform and were found to accumulate more COX-2 protein and have five times greater COX-2 activity than cells expressing both glycoforms. Thus, COX-2 turnover appears to depend upon glycosylation of the 72kDa glycoform.
Sevigny
Mary B
MB
Department of Natural Sciences and Mathematics, Dominican University of California, San Rafael, CA 94901, USA.
Li
Chai-Fei
CF
Alas
Monika
M
Hughes-Fulford
Millie
M
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001216:Asparagine / Q000235:genetics; D019556:COS Cells; D002522:Chlorocebus aethiops; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016296:Mutagenesis / Q000187:drug effects
D007527:Isoenzymes; D008565:Membrane Proteins; D016718:Arachidonic Acid; D001216:Asparagine; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human