A homeo-interaction sequence in the ectodomain of the fibroblast growth factor receptor

Fen Wang, Mikio Kan, Kerstin McKeehan, Jun Hyeog Jang, Shuju Feng, Wallace L. McKeehan

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Interaction of fibroblast growth factor receptors (FGFR) sufficient for a transphosphorylation event in which one intracellular domain is substrate for the other is essential for signal transduction. By analysis of the direct interaction of recombinant constructions co-expressed in baculoviral-infected insect cells, we identified a 17-amino acid sequence that is required for the stable interaction between ectodomains of FGFR. The sequence 160ERSPHRPILQAGLPANK176 (Glu160-Lys176) connects immunoglobulin modules II and III. In insect cells, the interaction between Glu160- Lys176 domains occurs independently of intact heparin or FGF binding domains. The sequence is not required for the binding of heparin or FGF-1, but is essential for mitogenic activity of the FGFR kinase in mammalian cells. The results support a model in which the homeo-interaction between Glu160-Lys176 in the ectodomain contributes to the interaction between intracellular domains in mammalian cell membranes (Kan, M., Wang, F., Kan, M, To, B., Gabriel, J. L, and McKeehan, W. L. (1996) J. Biol. Chem. 271, 26143- 26148). We propose that the Glu160Lys176 domain plays a pivotal role in restriction of the interaction between kinases by pericellular matrix heparan sulfate proteoglycan and divalent cations. Restrictions are overcome by FGF or constitutively by diverse gain of function mutations which cause skeletal and craniofacial abnormalities.

Original languageEnglish (US)
Pages (from-to)23887-23895
Number of pages9
JournalJournal of Biological Chemistry
Volume272
Issue number38
DOIs
StatePublished - Sep 19 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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