N-Glycosylation regulates fibroblast growth factor receptor/EGL-15 activity in Caenorhabditis elegans in vivo.
J Biol Chem
; 284(48): 33030-9, 2009 Nov 27.
Article
en En
| MEDLINE
| ID: mdl-19801543
ABSTRACT
The regulation of cell function by fibroblast growth factors (FGFs) classically occurs through a dual receptor system of a tyrosine kinase receptor (FGFR) and a heparan sulfate proteoglycan co-receptor. Mutations in some consensus N-glycosylation sites in human FGFR result in skeletal disorders and craniosynostosis syndromes, and biophysical studies in vitro suggest that N-glycosylation of FGFR alters ligand and heparan sulfate binding properties. The evolutionarily conserved FGFR signaling system of Caenorhabditis elegans has been used to assess the role of N-glycosylation in the regulation of FGFR signaling in vivo. The C. elegans FGF receptor, EGL-15, is N-glycosylated in vivo, and genetic substitution of specific consensus N-glycosylation sites leads to defects in the maintenance of fluid homeostasis and differentiation of sex muscles, both of which are phenotypes previously associated with hyperactive EGL-15 signaling. These phenotypes are suppressed by hypoactive mutations in EGL-15 downstream signaling components or activating mutations in the phosphatidylinositol 3-kinase pathway, respectively. The results show that N-glycans negatively regulate FGFR activity in vivo supporting the notion that mutation of N-glycosylation sites in human FGFR may lead to inappropriate activation of the receptor.
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1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Receptores de Factores de Crecimiento de Fibroblastos
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Caenorhabditis elegans
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Proteínas de Caenorhabditis elegans
Límite:
Animals
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Female
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Humans
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Male
Idioma:
En
Año:
2009
Tipo del documento:
Article