FIGURE 3.

Cell surface and extracellular molecules that interact with FGF ligands and receptors. FGFR showing immunoglobulin-like domains I, II, and III and intracellular tyrosine kinase domains, TK1 and TK2. FGF ligands bind to the heparan sulfate (HS) chains that decorate heparan sulfate proteoglycans (HSPGs). FGF ligands also bind to long pentraxin 3 (PTX3), FGF binding proteins (FGFBP), and latent TGFβ binding protein 2 (LTBP2). FGFR–FGF interactions are stabilized by HS, α, β, and ɣ Klotho, Anosmin 1 (ANOS1), and fibronectin leucine-rich transmembrane proteins (FLRTs). ANOS1 can form a complex with FGFR and L1 cell adhesion molecule (L1CAM). Cell adhesion molecules, including neural cell adhesion molecule (NCAM) and N-cadherin (CDH2) can activate low-level FGFR signaling independent of FGF ligands. Inorganic phosphate (Pi) can directly activate FGFR signaling independent of FGF ligands. FGF receptor-like 1 (FGFRL1) lacks an intracellular tyrosine kinase domain and is involved in cell adhesion and may act as a decoy receptor through binding FGF ligands. Relative strength of signaling is indicated below each receptor