Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family

Wilber Romero-fernandez, Dasiel O. Borroto-escuela, Alexander O. Tarakanov, Giuseppa Mudó, Manuel Narvaez, Mileidys Pérez-alea, Luigi F. Agnati, Francisco Ciruela, Natale Belluardo, Kjell Fuxe

Research output: Contribution to journalArticle

Abstract

Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the pres-ence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turntrigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in thecytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a signof FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligandson homodimer formation. A significant correlation between BRET2signaling and ERK1/2 phosphorylationwas observed, leading to a further characterization of the binding and signaling properties of the FGF sub-families. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control ofFGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformaticanalysis demonstrates the interface of the two pro-triplets SSS (Ser–Ser–Ser) and YGS (Tyr–Gly–Ser)located in the extracellular and intracellular domain of the FGFR1. These pro-triplets are postulated par-ticipate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonistligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodi-mer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appearsto have a distinct functional relevance.
Original languageEnglish
Pages (from-to)764-768
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number4
DOIs
Publication statusPublished - 1 Jun 2011

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    Romero-fernandez, W., Borroto-escuela, D. O., Tarakanov, A. O., Mudó, G., Narvaez, M., Pérez-alea, M., Agnati, L. F., Ciruela, F., Belluardo, N., & Fuxe, K. (2011). Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family. Biochemical and Biophysical Research Communications, 409(4), 764-768. https://doi.org/10.1016/j.bbrc.2011.05.085