FGFRL1 dimer binds FGFs

Stable Identifier
R-HSA-5654511
Type
Reaction [binding]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
Locations in the PathwayBrowser
General
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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, Trueb, B, Kälin, RE, Beyeler, M, Zhuang, L, Brändli, AW, Mullis, PE

J. Biol. Chem. 2010
18061161 The cell surface receptor FGFRL1 forms constitutive dimers that promote cell adhesion

Trueb, B, Rieckmann, T, Kotevic, I

Exp. Cell Res. 2008
22432025 Comparison of the gene expression profiles from normal and Fgfrl1 deficient mouse kidneys reveals downstream targets of Fgfrl1 signaling

Amann, R, Trueb, B, Gerber, SD, Wyder, S

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

Steinberg, F, Trueb, B, Beyeler, M, Villiger, PM, Gerber, SD

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

Kilkenny, DM, Rocheleau, JV, Altamentova, SM, Silva, PN

J. Biol. Chem. 2013
21616146 Interaction of the receptor FGFRL1 with the negative regulator Spred1

Trueb, B, Zhuang, L, Villiger, P

Cell. Signal. 2011
11418238 Identification of a new fibroblast growth factor receptor, FGFR5

Sleeman, M, Kumble, K, McDonald, M, Murison, JG, Watson, JD, White, D, Fraser, J, Yuan, S, Grandison, P

Gene 2001
23112089 Role of FGFRL1 and other FGF signaling proteins in early kidney development

Amann, R, Trueb, B, Gerber, SD

Cell. Mol. Life Sci. 2013
Participants
Participates
Orthologous Events
Authored
Reviewed
Created
Cite Us!