The fibroblast growth factor receptor acid box is essential for interactions with N-cadherin and all of the major isoforms of neural cell adhesion molecule.
Interactions between the neural cell adhesion molecules NCAM and N-cadherin with the fibroblast growth factor receptor (FGFR) are important for a number of developmental events and have also been implicated in tumor progression. The factors regulating these interactions are not known. We have used co-immunoprecipitation and co-clustering paradigms to show that both adhesion molecules can interact with the 3Ig IIIC isoform of the FGFR1 in a number of cell types. Interestingly, whereas the interaction can be seen over most of the cell surface, it is not seen at points of cell-cell contact where the adhesion molecules accumulate at stable junctions. We also demonstrate for the first time that all of the major isoforms of NCAM can interact with the FGFR. Using deletion mutagenesis we have found that the adhesion molecule/FGFR interaction can withstand the removal of most of any one of the FGFR immunoglobulin-like domains (D1-D3). In contrast, the FGFR interaction with N-cadherin and NCAM (but not FGF) is absolutely dependant on the presence of the acid box motif that can be found in the linker region between D1 and D2. As this motif can be spliced out of all four FGFRs, it suggests that this is one mechanism that can regulate the interaction of the receptor with different ligand classes.
Sanchez-Heras
Elena
E
Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom.
Howell
Fiona V
FV
Williams
Gareth
G
Doherty
Patrick
P
D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D005801:Genes, Homeobox; D006801:Humans; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D021381:Protein Transport; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism*
D015820:Cadherins; D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; D017468:Receptors, Fibroblast Growth Factor