Biology of FGFRL1, the fifth fibroblast growth factor receptor

Abstract

FGFRL1 (fibroblast growth factor receptor like 1) is the most recently discovered member of the FGFR family. It contains three extracellular Ig-like domains similar to the classical FGFRs, but it lacks the protein tyrosine kinase domain and instead contains a short intracellular tail with a peculiar histidine-rich motif. The gene for FGFRL1 is found in all metazoans from sea anemone to mammals. FGFRL1 binds to FGF ligands and heparin with high affinity. It exerts a negative effect on cell proliferation, but a positive effect on cell differentiation. Mice with a targeted deletion of the Fgfrl1 gene die perinatally due to alterations in their diaphragm. These mice also show bilateral kidney agenesis, suggesting an essential role for Fgfrl1 in kidney development. A human patient with a frameshift mutation exhibits craniosynostosis, arguing for an additional role of FGFRL1 during bone formation. FGFRL1 contributes to the complexity of the FGF signaling system.

Fibroblast Growth Factor Receptor Inhibitors as a Cancer Treatment: From a Biologic Rationale to Medical Perspectives

“…The cytoplasmic portion of FGFR1-4 contains a tyrosine kinase domain and a COOH tail. A fi fth receptor, FGFRL1, also binds FGFs, but it lacks the tyrosine kinase domain; moreover, FGFRL1 reportedly reduces cell growth and accelerates cell differentiation ( 3 ).…”

“…Understanding the mechanisms at the basis of these alterations and their multiple roles in cancer promotion and drug resistance is a fundamental step for further implementation of targeted therapies and research strategies. Cancer Discov;3(3); …”

SPATIAL DISTRIBUTION OF FIBROBLAST GROWTH FACTOR RECEPTOR 2 IN NORMAL AND LESIONED CENTRAL NERVOUS SYSTEM OF <I>PLEURODELES WALTLII</I>

“…FGF signaling is mediated by four types of receptors (FGFR1,FGFR2,FGFR3 and FGFR4), which all belong to the high affinity tyrosine kinase receptor family (Dionne et al, 1990;Keegan et al, 1991;Trueb, 2011). They are known to trigger the phosphorylation of signaling cascades and regulate protein synthesis and neuronal excitability.…”

Estudo das alterações na expressão gênica dos ependimomas

“…O gene FGFRL1 é membro da família de FGFR pouco conhecido, com domínio intracelular sem atividade tirosino-quinases (Trueb 2011 (Shimizu, Kagawa et al 2008;Steinberg, Zhuang et al 2010). Descrição inicial sugeria função na indução de adesão celular e suposto envolvimento na fusão célula-célula e formação de sincício (Trueb 2011).…”

“…Descrição inicial sugeria função na indução de adesão celular e suposto envolvimento na fusão célula-célula e formação de sincício (Trueb 2011). Há relatos de alteração desse gene em pacientes com cranioestenose (Rieckmann, Zhuang et al 2009), com hérnia diafragmática congênita (Holder, Klaassens et al 2007) e possível associação com a síndrome Wolf-Hirschhorn, que envolve alteração no crescimento, disgenesia facial, atraso no desenvolvimento e epilepsia com fenótipo variável, relacionada à deleção de parte do cromossomo 4p envolvendo a região de FGFRL1 (Catela, Bilbao-Cortes et al 2009).…”