Search

The biochemical and biophysical properties of mucinsare largely determined by extensive O-glycosylation of serine- andthreonine-rich tandem repeat (TR) domains. In a number of humandiseases aberrant O-glycosylation is associated with variationsin the properties of the cell surface–associated and secretedmucins. To evaluate in vivo the O-glycosylationof mucin TR domains, we generated recombinant chimeric mucins withTR sequences from MUC2, MUC4, MUC5AC, or MUC5B, which were substituted forthe native TRs of epitope-tagged MUC1 protein (MUC1F). These hybridmucins were extensively O-glycosylated and showed the expected associationwith the cell surface and release into culture media. The presenceof different TR domains within the chimeric mucins appears to have limitedinfluence on their posttranslational processing. Alterations inglycosylation were detailed by fast atom bombardment mass spectrometryand reactivity with antibodies against particular blood-group andtumor-associated carbohydrate antigens. Future applications of thesechimeras will include investigations of mucin posttranslationalmodification in the context of disease. [ABSTRACT FROM PUBLISHER]