PMID: 16274239

 

    Legend: Gene, Sites

Title : Functional effects of glycosylation at Asn-579 of the epidermal growth factor receptor

Abstract :
  1. We have investigated functional effects of glycosylation at N(579) of the epidermal growth factor receptor ( EGFR )
  2. Our previous study showed that the population of cell-surface expressed EGFRs in A431 cells, a human epidermoid carcinoma cell line, is composed of two subpopulations that differ by glycosylation at N(579) [Zhen et al. (2003) Biochemistry 42, 5478-5492]
  3. To characterize the subpopulation of receptors not glycosylated at N(579) , we established a 32D cell line expressing a point mutant of the EGFR (N579Q) N579Q ), which cannot be glycosylated at this position
  4. Analysis of epitope accessibility suggests that the lack of glycosylation at N(579) weakens auto-inhibitory tether interactions, and cross-linking experiments suggest a somewhat elevated level of preformed N579Q- EGFR dimers in the absence of ligand relative to wild-type EGFR ( WT-EGFR )
  5. However, ligand drives the majority of N579Q- EGFR dimerization , suggesting that untethering, while necessary, is not sufficient to drive dimerization
  6. Ligand-binding experiments reveal a much greater fraction of N579Q-EGFRs in a high-affinity state compared to the fraction of WT-EGFRs in a high-affinity state
  7. However, differences in the kinetic association and dissociation rates indicate that the high-affinity states of the WT and the N579Q receptors are distinct
  8. EGF-stimulated phosphorylation in cells expressing N579Q-EGFRs results in notable differences in the pattern of tyrosine phosphorylated proteins compared with that obtained in cells expressing WT-EGFRs
  9. Moreover, although WT-EGFRs confer cell survival in 32D cells in the absence of interleukin-3 and EGF , we found that receptors lacking glycosylation at N(579) do not
  10. This is the first study of which we are aware to show that selective glycosylation of a specific N-glycosylation site can produce two functionally distinct receptors
Output (sent_index, trigger, protein, sugar, site):
  • 1. glycosylation, , -, -, N(579)
  • 10. N-glycosylation, , -, -, site
  • 10. glycosylation, , -, -, site
  • 3. glycosylated, , -, -, N(579)
  • 3. glycosylated, , EGFR (N579Q), -, position
  • 3. glycosylated, , receptors, -, N(579)
  • 4. glycosylation, , -, -, N(579)
  • 9. glycosylation, , -, -, N(579)
Output(Part-Of) (sent_index, protein, site):
  • 0. epidermal growth factor receptor, Asn-579
  • 1. epidermal growth factor receptor, N(579)
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 1. epidermal growth factor receptor, -, N(579)
  • 3. epidermal growth factor receptor, -, N(579)
  • 3. receptors, -, N(579)
  • 4. epidermal growth factor receptor, -, N(579)
  • 9. epidermal growth factor receptor, -, N(579)

 

 

Protein NCBI ID SENTENCE INDEX
EGFR dimerization 13649 5
EGFR (N579Q) 13649 3
EGFR 13649 1,4
WT-EGFR 13649 4
EGFR dimers 13649 4
interleukin-3 and EGF 16187 9
epidermal growth factor receptor 13649 0,1
EGF 13645 8