FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism

Lijuan He, Nadia Shobnam, William C. Wimley, Kalina A Hristova

Research output: Contribution to journalArticle

Abstract

The G380R mutation in the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) causes achondroplasia, the mostcommonform of human dwarfism. Achondroplasia is a heterozygous disorder, and thus the affected individuals express both wild-type and mutant FGFR3. Yet heterodimerization in achondroplasia has not been characterized thus far. To investigate the formation of FGFR3 heterodimers in cellular membranes we designed an FGFR3 construct that lacks the kinase domain, and we monitored the formation of inactive heterodimers between this construct and wild-type and mutant FGFR3. The formation of the inactive heterodimers depleted the pool of full-length receptors capable of forming active homodimers and ultimately reduced their phosphorylation. By analyzing the effect of the truncated FGFR3 on full-length receptor phosphorylation, we demonstrated that FGFR3 WT/G380R heterodimers form with lower probability than wild-type FGFR3 homodimers at low ligand concentration. These results further our knowledge of FGFR3-associated bone disorders.

Original languageEnglish (US)
Pages (from-to)13272-13281
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number15
DOIs
StatePublished - Apr 15 2011

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Receptor, Fibroblast Growth Factor, Type 3
Achondroplasia
Dwarfism
Phosphorylation
Bone
Phosphotransferases

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism. / He, Lijuan; Shobnam, Nadia; Wimley, William C.; Hristova, Kalina A.

In: Journal of Biological Chemistry, Vol. 286, No. 15, 15.04.2011, p. 13272-13281.

Research output: Contribution to journalArticle

He, Lijuan ; Shobnam, Nadia ; Wimley, William C. ; Hristova, Kalina A. / FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 15. pp. 13272-13281.
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