Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II

A severe form of human achondroplasia

Changsheng Guo, Catherine R. Degnin, Melanie B. Laederich, Gregory P. Lunstrum, Paul Holden, Jeanie Bihlmaier, Deborah Krakow, Yoon-Jae Cho, William A. Horton

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Thanatophoric dysplasia is a member of the achondroplasia family of human skeletal dysplasias, which result from FGFR3 mutations that exaggerate this receptor's inhibitory influence on chondrocyte proliferation and differentiation in the skeletal growth plate. We have previously reported that defective lysosomal degradation of activated receptor contributes to the gain-of-function of the mutant FGFR3. We now provide evidence that this disturbance is mediated by the receptor's kinase activity and involves constitutive induction and activation of Spry2. Our findings suggest that activated Spry2 may interfere with c-Cbl-mediated ubiquitination of FGFR3 by sequestering c-Cbl. They provide novel insight into the pathogenesis of this group of human skeletal dysplasias and identify a mechanism that potentially could be targeted therapeutically.

Original languageEnglish (US)
Pages (from-to)1471-1477
Number of pages7
JournalCellular Signalling
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

Thanatophoric Dysplasia
Achondroplasia
Growth Plate
Ubiquitination
Chondrocytes
Phosphotransferases
Mutation

Keywords

  • Achondroplasia
  • c-Cbl
  • FGFR3
  • Receptor degradation
  • RTK
  • Sprouty
  • Thanatophoric dysplasia

ASJC Scopus subject areas

  • Cell Biology

Cite this

Guo, C., Degnin, C. R., Laederich, M. B., Lunstrum, G. P., Holden, P., Bihlmaier, J., ... Horton, W. A. (2008). Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II: A severe form of human achondroplasia. Cellular Signalling, 20(8), 1471-1477. https://doi.org/10.1016/j.cellsig.2008.04.001

Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II : A severe form of human achondroplasia. / Guo, Changsheng; Degnin, Catherine R.; Laederich, Melanie B.; Lunstrum, Gregory P.; Holden, Paul; Bihlmaier, Jeanie; Krakow, Deborah; Cho, Yoon-Jae; Horton, William A.

In: Cellular Signalling, Vol. 20, No. 8, 01.08.2008, p. 1471-1477.

Research output: Contribution to journalArticle

Guo, C, Degnin, CR, Laederich, MB, Lunstrum, GP, Holden, P, Bihlmaier, J, Krakow, D, Cho, Y-J & Horton, WA 2008, 'Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II: A severe form of human achondroplasia', Cellular Signalling, vol. 20, no. 8, pp. 1471-1477. https://doi.org/10.1016/j.cellsig.2008.04.001
Guo, Changsheng ; Degnin, Catherine R. ; Laederich, Melanie B. ; Lunstrum, Gregory P. ; Holden, Paul ; Bihlmaier, Jeanie ; Krakow, Deborah ; Cho, Yoon-Jae ; Horton, William A. / Sprouty 2 disturbs FGFR3 degradation in thanatophoric dysplasia type II : A severe form of human achondroplasia. In: Cellular Signalling. 2008 ; Vol. 20, No. 8. pp. 1471-1477.
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