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

Fingerprint

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

Cite this

Romero-fernandez, W., Borroto-escuela, D. O., Tarakanov, A. O., Mudó, G., Narvaez, M., Pérez-alea, M., ... 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
Romero-fernandez, Wilber ; Borroto-escuela, Dasiel O. ; Tarakanov, Alexander O. ; Mudó, Giuseppa ; Narvaez, Manuel ; Pérez-alea, Mileidys ; Agnati, Luigi F. ; Ciruela, Francisco ; Belluardo, Natale ; 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, No. 4. pp. 764-768.
@article{6f50c0a2aeb444ff834b78c5e8d37b3e,
title = "Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family",
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.",
author = "Wilber Romero-fernandez and Borroto-escuela, {Dasiel O.} and Tarakanov, {Alexander O.} and Giuseppa Mud{\'o} and Manuel Narvaez and Mileidys P{\'e}rez-alea and Agnati, {Luigi F.} and Francisco Ciruela and Natale Belluardo and Kjell Fuxe",
year = "2011",
month = "6",
day = "1",
doi = "10.1016/j.bbrc.2011.05.085",
language = "English",
volume = "409",
pages = "764--768",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "4",

}

Romero-fernandez, W, Borroto-escuela, DO, Tarakanov, AO, Mudó, G, Narvaez, M, Pérez-alea, M, Agnati, LF, 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, vol. 409, no. 4, pp. 764-768. https://doi.org/10.1016/j.bbrc.2011.05.085

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

In: Biochemical and Biophysical Research Communications, Vol. 409, No. 4, 01.06.2011, p. 764-768.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family

AU - Romero-fernandez, Wilber

AU - Borroto-escuela, Dasiel O.

AU - Tarakanov, Alexander O.

AU - Mudó, Giuseppa

AU - Narvaez, Manuel

AU - Pérez-alea, Mileidys

AU - Agnati, Luigi F.

AU - Ciruela, Francisco

AU - Belluardo, Natale

AU - Fuxe, Kjell

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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.

AB - 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.

UR - http://linkinghub.elsevier.com/retrieve/pii/S0006291X11008527

U2 - 10.1016/j.bbrc.2011.05.085

DO - 10.1016/j.bbrc.2011.05.085

M3 - Article

VL - 409

SP - 764

EP - 768

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 0006-291X

IS - 4

ER -