NCAM-derived peptides function as agonists for the fibroblast growth factor receptor.
The neural cell adhesion molecule (NCAM) directly interacts with the fibroblast growth factor receptor (FGFR). Both fibronectin type III (FN3) modules of NCAM are involved in this interaction. One of the NCAM-FGFR contact sites has been localized recently to the upper N-terminal part of the second NCAM FN3 module encompassing the F and G beta-strands and the interconnecting loop region. Here, we investigated whether any of the six putative strand-loop-strand regions in the first NCAM FN3 module are involved in FGFR interactions. Peptide sequences encompassing these regions, termed encamins, were synthesized and tested for their ability to bind and activate FGFR. Encamins localized to the N-terminal part of the first FN3 module did not interact with FGFR, whereas encamins localized to the C-terminal part, termed EncaminA, C and E, bound to and activated FGFR. The encamins induced FGFR-dependent neurite outgrowth, and EncaminC and E promoted neuronal survival and enhanced pre-synaptic function. In conclusion, the interaction between NCAM and FGFR probably involves multiple contact sites at an interface formed by the two NCAM FN3 modules and FGFR, and encamins could constitute important pharmacological tools for the study of specific functional aspects of NCAM, including neuroprotection and modulation of plasticity.
Hansen
Stine M M
SM
Protein Laboratory, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
Køhler
Lene B
LB
Li
Shizhong
S
Kiselyov
Vladislav
V
Christensen
Claus
C
Owczarek
Sylwia
S
Bock
Elisabeth
E
Berezin
Vladimir
V
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000819:agonists* / Q000378:metabolism*
D019006:Neural Cell Adhesion Molecules; D010455:Peptides; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors