FGFR is one of the heterophilic interactors of NCAM. The FG loop region of the second Fn3 module of NCAM binds to Ig domains 2 and 3 of FGFR. The FGFR binding site to NCAM overlaps with the site of NCAM-ATP interaction, and ATP is capable of disrupting NCAM-FGFR binding and signaling.
The interaction of NCAM activates FGFR and NCAM might merely mimic FGF's in FGFR stimulation, but there is a difference in the activation pattern induced by NCAM and FGF-2. NCAM activated FGFR stimulates neurite outgrowth by stimulating PLCgamma and DAG lipase leading to generation of arachidonic acid.