PMID: 24018687

 

    Legend: Sugar

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 :

1. 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
2. Cycloheximide time-course experiments revealed that the high-molecular-mass forms of DDR1 and DDR2 were significantly less stable than control receptor tyrosine kinases
3. 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
4. Taken together, these results suggest a mechanism to control the activity of the DDR family by regulating its cell-surface expression
5. 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