"The novel protein contained three extracellular Ig-like domains that were related to the members of the fibroblast growth factor (FGF) receptor family. However, it lacked the intracellular protein tyrosine kinase domain required for signal transduction by transphosphorylation."

"Similar to FGF receptors, the expressed protein interacted specifically with heparin and with FGF2."

"When expressed in cultured cells as a fusion protein with green fluorescent protein, FGFRL1 was specifically localized to the plasma membrane where it might interact with FGF ligands."

"When overexpressed in MG-63 osteosarcoma cells, the novel receptor had a negative effect on cell proliferation. Taken together our data are consistent with the view that FGFRL1 acts as a decoy receptor for FGF ligands."

"FGFRL1 was expressed preferentially in skeletal tissues as demonstrated by Northern blotting and in situ hybridization."

"Utilizing the FRET (fluorescence resonance energy transfer) technique, we demonstrate that FGFRL1 forms constitutive homodimers at cell surfaces. The formation of homodimers was verified by co-precipitation of differentially tagged FGFRL1 polypeptides from solution."

"If overexpressed in cultivated cells, FGFRL1 was found to be enriched at cell-cell contact sites."

"The extracellular domain of recombinant FGFRL1 promoted cell adhesion, but not cell spreading, when coated on plastic surfaces."

"Adhesion was mediated by heparan sulfate glycosaminoglycans located at the cell surface. It could specifically be blocked by addition of soluble heparin but not by addition of other glycosaminoglycans."

"With its dimeric structure and its adhesion promoting properties, FGFRL1 resembles the nectins, a family of cell adhesion molecules found at cell-cell junctions."

"When the amino acid sequence of the putative heparin-binding site was modified by in vitro mutagenesis, the resulting protein exhibited decreased affinity for heparin and reduced activity in the cell-binding assay."

"Its extracellular domain is very similar to FGFR1-4 and binds FGFs, such as FGF-2 and FGF-8, with high affinity. In contrast to FGFR1-4, the intracellular tyrosine kinase domain of FGFRL1 is replaced by a short histidine-rich C-terminal tail, which is unable to convey canonical signal transduction through receptor auto-phosphorylation"

"Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1"

"Overexpression of FGFRL1 effectively attenuated the phosphorylation of FGFR-substrate 2α (FRS2α), which is typically activated by FGFs including FGF8b (Figure 3A,C, upper panel) [6]"

"In non-malignant tissues (BPH and AdjPr), luminal epithelial cells showed clear membrane-associated FGFRL1 staining, often in combination with weak cytoplasmic staining (Figure 1A,B). In HGPIN and primary PCa, membranous staining was less clear, but increased cytoplasmic and positive nuclear staining were often observed (Figure 1C,D)"

"It also binds to SHP-1 phosphatase in pancreatic islet beta cells, which may affect cellular signaling [17] and negatively acting Spread 1, a member of the Sprouty/Spread family [18]"

"In mesenchymal cells, FGFRL1 inhibits cell proliferation [22], is associated with cell differentiation [22,23], and induces cell adhesion [24,25]"

"Fgfrl1 knock-out mice die shortly after birth due to malformation of the diaphragm. The mutant diaphragm muscle obviously is not strong enough to inflate the lungs after birth. However, the most striking phenotype of the Fgfrl1 deficient mice is the nearly complete absence of the metanephric kidneys"

"Utilizing organ cultures and different staining techniques, we demonstrated that Fgfrl1 deficiency leads to a dramatic reduction of ureteric branching and to a lack of mesenchymal-to-epithelial transition in the nephrogenic mesenchyme"

"At E12.5, Fgfrl1 mRNA was highly expressed in the metanephric mesenchyme and in the ureteric bud. At E14.5, strong Fgfrl1 signal was detected in nascent nephrons and in the metanephric mesenchyme. At E18.5, Fgfrl1 signal was primarily found in tubules and nephrons"

"The extracellular domain of Fgfrl1 interacts with heparin [13] and with Fgf ligands, primarily Fgf-2, -3, -4, -8, and -22 [14]"

"Many of these genes are involved in the Fgf/Fgfr, Wnt/ß-catenin, Bmp, Notch, and Six/Eya/Dach signaling pathway"

"Here we used the yeast two-hybrid system to demonstrate that FGFRL1 binds with its C-terminal, histidine-rich domain to Spred1 and to other proteins of the Sprouty/Spred family"

"Truncation experiments further showed that FGFRL1 interacts with the SPR domain of Spred1, a domain that is shared by all members of the Sprouty/Spred family"

"Interestingly, Spred1 increased the retention time of FGFRL1 at the plasma membrane where the receptor might interact with ligands"

"FGFRL1 is a member of the fibroblast growth factor receptor family. It plays an essential role during branching morphogenesis of the metanephric kidneys, as mice with a targeted deletion of the Fgfrl1 gene show severe kidney dysplasia"

"FGFRL1 binds to SPRED1 and 2 and Sprouty1 as assessed by co-immunoprecipitation"

"The interaction requires the C-terminal residues of the short intracellular domain of FGFRL1"

"The SPRED proteins are members of the Sprouty family, with established roles as negative regulators of the Ras/Raf/Erk signaling pathway"

"FGFRL1 forms constitutive dimers and has been shown to bind to a wide range of FGF ligands, including FGF3,4,8,10, 22"

"and with lower affinity to FGF2,5,17,18 and 23"

"FGFRL1 lacks the internal kinase domain required for typical downstream FGFR signaling"

"FGFRL1 has been postulated to act as a decoy receptor that sequesters ligand away from canonical FGF receptors"

"FGFRL1 knockout mice die shortly after birth from lung and renal defects"

"FGFRL1 is an evolutionarily ancient gene present across a broad range of metazoans. Orthologs have been identified in species from cnidarians (e.g. Nematostella sea anemone) to vertebrates"

"Its extracellular portion consists of three Ig-like domains (D1, D2, D3), arranged similarly to FGFR1-4... Crucially, FGFRL1 lacks any kinase or other conventional signaling domain intracellularly"

"FGFRL1 can thus be viewed as a multifunctional surface protein: part decoy receptor (binding and neutralizing FGFs), part adhesion molecule (connecting cells via Ig domain interactions), and part fusogen (in specific contexts causing membrane merging)"

"The most striking phenotypes are absence of kidneys, a malformed diaphragm, and a dome-shaped skull"

"A set of four hydrophobic residues in Ig3 (e.g. L281, F303, L339, V304 in human FGFRL1) form a pocket that likely interacts with a target protein on adjacent cells"

"In normal FGFRL1, these signals mediate rapid trafficking of the receptor from the plasma membrane into endosomes and lysosomes... Like many membrane receptors, FGFRL1 can be proteolytically shed from the cell surface"