Reactome | FGFRL1 dimer binds FGFs

FGFRL1 dimer binds FGFs

Stable Identifier

R-HSA-5654511

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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FGFRL1 is a fifth member of the FGFR family of receptors that shares 40% sequence similarity with the extracellular region of FGFR1-4, but FGFRL1 lacks the internal kinase domain required for typical downstream FGFR signaling. Instead, FGFRL1 has a short intracellular domain with a C-terminal histidine rich region that has been shown to interact with the MAP kinase regulator SPRED proteins (Sleeman et al, 2001; Zhuang et al, 2011; reviewed in Trueb et al, 2013). 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 (Reickman et al, 2008; Steinberg et al, 2010). FGFRL1 knockout mice die shortly after birth from lung and renal defects (Gerber et al, 2009; Gerber et al, 2012; Trueb et al, 2013). FGFRL1 has been postulated to act as a decoy receptor that sequesters ligand away from canonical FGF receptors; more recently, however, alternate roles for FGFRL1 in enhancing ERK1/2 activation or promoting FGFR1-mediated signaling have been suggested (Sleeman et al, 2001; Steinberg et al, 2010; Silva et al, 2013; Amann and Trueb, 2013). Further work will be required to elucidate the role(s) of FGFRL1.

Literature References

PubMed ID	Title	Journal	Year
19920134	The FGFRL1 receptor is shed from cell membranes, binds fibroblast growth factors (FGFs), and antagonizes FGF signaling in Xenopus embryos Steinberg, F, Zhuang, L, Beyeler, M, Kälin, RE, Mullis, PE, Brändli, AW, Trueb, B	J. Biol. Chem.	2010
18061161	The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion Rieckmann, T, Kotevic, I, Trueb, B	Exp. Cell Res.	2008
22432025	Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling Gerber, SD, Amann, R, Wyder, S, Trueb, B	PLoS ONE	2012
24026051	Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1 Amann, R, Trueb, B	Int. J. Mol. Med.	2013
19715689	The murine Fgfrl1 receptor is essential for the development of the metanephric kidney Gerber, SD, Steinberg, F, Beyeler, M, Villiger, PM, Trueb, B	Dev. Biol.	2009
23640895	Fibroblast growth factor receptor like-1 (FGFRL1) interacts with SHP-1 phosphatase at insulin secretory granules and induces beta-cell ERK1/2 protein activation Silva, PN, Altamentova, SM, Kilkenny, DM, Rocheleau, JV	J. Biol. Chem.	2013
21616146	Interaction of the receptor FGFRL1 with the negative regulator Spred1 Zhuang, L, Villiger, P, Trueb, B	Cell. Signal.	2011
11418238	Identification of a new fibroblast growth factor receptor, FGFR5 Sleeman, M, Fraser, J, McDonald, M, Yuan, S, White, D, Grandison, P, Kumble, K, Watson, JD, Murison, JG	Gene	2001
23112089	Role of FGFRL1 and other FGF signaling proteins in early kidney development Trueb, B, Amann, R, Gerber, SD	Cell. Mol. Life Sci.	2013