The physical basis of FGFR3 response to fgf1 and fgf2

Fenghao Chen, Kalina A Hristova

Research output: Contribution to journalArticle

Abstract

Fibroblast growth factors (fgfs) play important roles in embryonic development and in adult life by controlling cell proliferation, differentiation, and migration. There are 18 known fgfs which activate four fibroblast growth factor receptors (FGFRs), with different isoforms due to alternative splicing. The physical basis behind the specificity of the biological responses mediated by different fgf-FGFR pairs is currently unknown. To gain insight into the specificity of FGFR3c, a membrane receptor which is critical for bone development, we studied, analyzed, and compared the activation of FGFR3c over a wide range of fgf1 and fgf2 concentrations. We found that while the strength of fgf2 binding to FGFR3c is lower than the strength of fgf1 binding, the fgf2-bound dimers exhibit higher phosphorylation of the critical tyrosines in the activation loop. As a result, fgf1 and fgf2 elicit a similar FGFR3c response at low, but not at high, concentrations. The results demonstrate the versatility of FGFR3c response to fgf1 and fgf2 and highlight the complexity in fgf signaling.

Original languageEnglish (US)
Pages (from-to)8576-8582
Number of pages7
JournalBiochemistry®
Volume50
Issue number40
DOIs
StatePublished - Oct 11 2011

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Fibroblast Growth Factors
Fibroblast Growth Factor Receptors
Chemical activation
Phosphorylation
Bone Development
Cell proliferation
Alternative Splicing
Dimers
Embryonic Development
Cell Movement
Tyrosine
Cell Differentiation
Protein Isoforms
Bone
Cell Proliferation
Membranes

ASJC Scopus subject areas

  • Biochemistry

Cite this

The physical basis of FGFR3 response to fgf1 and fgf2. / Chen, Fenghao; Hristova, Kalina A.

In: Biochemistry®, Vol. 50, No. 40, 11.10.2011, p. 8576-8582.

Research output: Contribution to journalArticle

Chen, Fenghao ; Hristova, Kalina A. / The physical basis of FGFR3 response to fgf1 and fgf2. In: Biochemistry®. 2011 ; Vol. 50, No. 40. pp. 8576-8582.
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