Molecular Biology Reports

, Volume 36, Issue 4, pp 631–639 | Cite as

Epidermal growth factor receptors: function modulation by phosphorylation and glycosylation interplay

  • Afshan Kaleem
  • Ishtiaq Ahmad
  • Daniel C. Hoessli
  • Evelyne Walker-Nasir
  • Muhammad Saleem
  • Abdul Rauf Shakoori
  • Nasir-ud-Din


Post-translational modifications (PTMs) of proteins induce structural and functional changes that are most often transitory and difficult to follow and investigate in vivo. In silico prediction procedures for PTMs are very valuable to foresee and define such transitory changes responsible for the multifunctionality of proteins. Epidermal growth factor receptor (EGFR) is such a multifunctional transmembrane protein with intrinsic tyrosine kinase activity that is regulated primarily by ligand-stimulated transphosphorylation of dimerized receptors. In human EGFR, potential phosphorylation sites on Ser, Thr and Tyr residues including five autophosphorylation sites on Tyr were investigated using in silico procedures. In addition to phosphorylation, O-GlcNAc modifications and interplay between these two modifications was also predicted. The interplay of phosphorylation and O-GlcNAc modification on same or neighboring Ser/Thr residues is termed as Yin Yang hypothesis and the interplay sites are named as Yin Yang sites. Amongst these modification sites, one residue is localized in the juxtamembrane (Thr 654) and two are found in the catalytic domain (Ser 1046/1047) of the EGFR. We propose that, when EGFR is O-GlcNAc modified on Thr 654, EGFR may be transferred from early to late endosomes, whereas when EGFR is O-GlcNAc modified on Ser 1046/1047 desensitization of the receptor may be prevented. These findings suggest a complex interplay between phosphorylation and O-GlcNAc modification resulting in modulation of EGFR’s functionality.


Epidermal growth factor receptor Phosphorylation O-GlcNAc modification Lysosomal targeting Desensitization 



Nasir-ud-Din acknowledges support from Pakistan Academy of Sciences for this work.


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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Afshan Kaleem
    • 1
  • Ishtiaq Ahmad
    • 1
  • Daniel C. Hoessli
    • 2
  • Evelyne Walker-Nasir
    • 1
  • Muhammad Saleem
    • 3
  • Abdul Rauf Shakoori
    • 4
  • Nasir-ud-Din
    • 1
    • 5
    • 6
  1. 1.Institute of Molecular Sciences and BioinformaticsLahorePakistan
  2. 2.Department of Pathology and Immunology, CMUUniversity of GenevaGenevaSwitzerland
  3. 3.Department of BotanyUniversity of the PunjabLahorePakistan
  4. 4.School of Biological SciencesUniversity of the PunjabLahorePakistan
  5. 5.HEJ Research Institute of ChemistryUniversity of KarachiKarachiPakistan
  6. 6.Institute of Management Sciences, University of GenevaGenevaSwitzerland

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