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

Natale Belluardo, Giuseppa Mudo', Francisco Ciruela, Alexander O. Tarakanov, Mileidys Pérez-Alea, Luigi F. Agnati, Dasiel O. Borroto-Escuela, Manuel Narvaez, Wilber Romero-Fernandez, Kjell Fuxe

Risultato della ricerca: Article

18 Citazioni (Scopus)

Abstract

Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turn trigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in the cytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a sign of FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligands on homodimer formation. A significant correlation between BRET(2) signaling and ERK1/2 phosphorylation was observed, leading to a further characterization of the binding and signaling properties of the FGF subfamilies. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control of FGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformatic analysis 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 participate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonist ligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodimer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appears to have a distinct functional relevance.
Lingua originaleEnglish
pagine (da-a)564-568
Numero di pagine5
RivistaBiochemical and Biophysical Research Communications
Volume409
Stato di pubblicazionePublished - 2011

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Receptor, Fibroblast Growth Factor, Type 1
Bioluminescence
Ligands
Energy Transfer
Genes
Phosphorylation
Heparitin Sulfate
Bioinformatics
Glycosaminoglycans
Computational Biology
Tyrosine

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Cell Biology
  • Molecular Biology
  • Biochemistry

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Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family. / Belluardo, Natale; Mudo', Giuseppa; Ciruela, Francisco; Tarakanov, Alexander O.; Pérez-Alea, Mileidys; Agnati, Luigi F.; Borroto-Escuela, Dasiel O.; Narvaez, Manuel; Romero-Fernandez, Wilber; Fuxe, Kjell.

In: Biochemical and Biophysical Research Communications, Vol. 409, 2011, pag. 564-568.

Risultato della ricerca: Article

Belluardo, N, Mudo', G, Ciruela, F, Tarakanov, AO, Pérez-Alea, M, Agnati, LF, Borroto-Escuela, DO, Narvaez, M, Romero-Fernandez, W & Fuxe, K 2011, 'Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family.', Biochemical and Biophysical Research Communications, vol. 409, pagg. 564-568.
Belluardo, Natale ; Mudo', Giuseppa ; Ciruela, Francisco ; Tarakanov, Alexander O. ; Pérez-Alea, Mileidys ; Agnati, Luigi F. ; Borroto-Escuela, Dasiel O. ; Narvaez, Manuel ; Romero-Fernandez, Wilber ; Fuxe, Kjell. / Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family. In: Biochemical and Biophysical Research Communications. 2011 ; Vol. 409. pagg. 564-568.
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abstract = "Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turn trigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in the cytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a sign of FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligands on homodimer formation. A significant correlation between BRET(2) signaling and ERK1/2 phosphorylation was observed, leading to a further characterization of the binding and signaling properties of the FGF subfamilies. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control of FGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformatic analysis 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 participate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonist ligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodimer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appears to have a distinct functional relevance.",
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T1 - Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family.

AU - Belluardo, Natale

AU - Mudo', Giuseppa

AU - Ciruela, Francisco

AU - Tarakanov, Alexander O.

AU - Pérez-Alea, Mileidys

AU - Agnati, Luigi F.

AU - Borroto-Escuela, Dasiel O.

AU - Narvaez, Manuel

AU - Romero-Fernandez, Wilber

AU - Fuxe, Kjell

PY - 2011

Y1 - 2011

N2 - Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turn trigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in the cytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a sign of FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligands on homodimer formation. A significant correlation between BRET(2) signaling and ERK1/2 phosphorylation was observed, leading to a further characterization of the binding and signaling properties of the FGF subfamilies. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control of FGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformatic analysis 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 participate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonist ligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodimer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appears to have a distinct functional relevance.

AB - Fibroblast growth factor receptor 1 (FGFR1) is known to be activated by homodimerization in the presence of both the FGF agonist ligand and heparan sulfate glycosaminoglycan. FGFR1 homodimers in turn trigger a variety of downstream signaling cascades via autophosphorylation of tyrosine residues in the cytoplasmic domain of FGFR1. By means of Bioluminescence Energy Resonance Transfer (BRET) as a sign of FGFR1 homodimerization, we evaluated in HEK293T cells the effects of all known FGF agonist ligands on homodimer formation. A significant correlation between BRET(2) signaling and ERK1/2 phosphorylation was observed, leading to a further characterization of the binding and signaling properties of the FGF subfamilies. FGF agonist ligand-FGFR1 binding interactions appear as the main mechanism for the control of FGFR1 homodimerization and MAPK signaling which demonstrated a high correlation. The bioinformatic analysis 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 participate in the FGFR1 homodimerization interface interaction. The findings also reveal that FGF agonist ligands within the same subfamily of the FGF gene family produced similar increases in FGFR1 homodimer formation and MAPK signaling. Thus, the evolutionary relationship within this gene family appears to have a distinct functional relevance.

KW - Fibroblast growth factors, FGFR1, Homodimerization, BRET, MAPK

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