FGF receptors ubiquitylation: Dependence on tyrosine kinase activity and role in downregulation

E. Monsonego-Ornan, R. Adar, E. Rom, A. Yayon*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


A crucial aspect of ligand-mediated receptor activation and shut-down is receptor internalization and degradation. Here we compared the ubiquitylation of either wild type or a K508A 'kinase-dead' mutant of fibroblast growth factor receptor 3 (FGFR3) with that of its naturally occurring overactive mutants, G380R as in achondroplasia, or K650E involved in thanatophoric dysplasia. Fibroblast growth factor receptors ubiquitylation was found to be directly proportional to their intrinsic tyrosine kinase activity, both of which could be blocked using kinase inhibitors. Despite excessive ubiquitylation, both overactive mutants failed to be efficiently degraded, even when challenged with ligand or overexpression of c-Cbl, a putative E3 ligase. We conclude that phosphorylation is essential for FGFR3 ubiquitylation, but is not sufficient to induce downregulation of its internalization resistant mutants.

Original languageAmerican English
Pages (from-to)83-89
Number of pages7
JournalFEBS Letters
Issue number1-3
StatePublished - 25 Sep 2002
Externally publishedYes


  • Achondroplasia
  • E3 ligase
  • Internalization
  • Thanatophoric dysplasia
  • Tyrosine kinase receptors


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