Fibronectin type III (FN3) modules of the neuronal cell adhesion molecule L1 interact directly with the fibroblast growth factor (FGF) receptor.
The neuronal cell adhesion molecule (CAM) L1 promotes axonal outgrowth, presumably through an interaction with the fibroblast growth factor receptor (FGFR). The present study demonstrates a direct interaction between L1 fibronectin type III (FN3) modules I-V and FGFR1 immunoglobulin (Ig) modules II and III by surface plasmon resonance analysis. Binding of L1 to FGFR1 was enhanced by adenosine 5'-triphosphate (ATP), adenylylmethylenediphosphonate (AMP-PCP), and guanosine-5'-triphosphate (GTP), but not adenosine monophosphate (AMP). The L1-FN3 modules were capable of activating FGFR1, reflected by receptor phosphorylation, and this resulted in the induction of differentiation of primary neurons, reflected by neurite outgrowth. Furthermore, ATP modulated L1-induced neuronal differentiation and FGFR1 phosphorylation through regulation of the L1-FGFR1 interaction.
Kulahin
Nikolaj
N
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. kulahin@plab.ku.dk
Li
Shizhong
S
Hinsby
Anders
A
Kiselyov
Vladislav
V
Berezin
Vladimir
V
Bock
Elisabeth
E
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005353:Fibronectins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats
D005353:Fibronectins; D039842:Neural Cell Adhesion Molecule L1; D000266:Adenylyl Imidodiphosphate; D005346:Fibroblast Growth Factors; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate