title: Low stability and a conserved N-glycosylation site are associated with regulation of the discoidin domain receptor family by glucose via post-translational N-glycosylation.
abstract: Cell-surface expression of the discoidin domain receptor (DDR) tyrosine kinase family in high molecular mass form was controlled sensitively by the glucose concentration through a post-translational N-glycosylation process. Cycloheximide time-course experiments revealed that the high-molecular-mass forms of DDR1 and DDR2 were significantly less stable than control receptor tyrosine kinases. Site-directed mutational analysis of the consensus N-glycosylation sites of the DDRs revealed that mutations of asparagine 213 of DDR2 and asparagine 211 of DDR1, a conserved N-glycosylation site among vertebrate DDRs, inhibited the generation of the high-molecular-mass isoform. Taken together, these results suggest a mechanism to control the activity of the DDR family by regulating its cell-surface expression. Due to low stability, the steady-state population of functional DDR proteins in the cell surface depends sensitively on its maturation process via post-translational N-glycosylation, which is controlled by the glucose supply and the presence of a conserved N-glycosylation site.
authors.affiliation: Future Fusion Research Division, Korea Institute of Science and Technology.
authors.forename: Trong Nhat
authors.initials: TN
authors.lastname: Phan
authors.forename: Ee Lin
authors.initials: EL
authors.lastname: Wong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Sun
authors.forename: Geunwoong
authors.initials: G
authors.lastname: Kim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Jung
authors.forename: Chang No
authors.initials: CN
authors.lastname: Yoon
authors.forename: Beom-Seok
authors.initials: BS
authors.lastname: Yang
mesh_terms: D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D017124:Conserved Sequence; D000070818:Discoidin Domain Receptors; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects*; D006801:Humans; D008297:Male; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000096:biosynthesis; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D055550:Protein Stability / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D011134:Polysaccharides; D020033:Protein Isoforms; D011975:Receptors, Mitogen; D003094:Collagen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D005947:Glucose