FGFR1 ligand binding and activation

Stable Identifier
R-HSA-190242
Type
Pathway
Species
Homo sapiens
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The vertebrate fibroblast growth factor receptor 1 (FGFR1) is alternatively spliced generating multiple variants that are differentially expressed during embryo development and in the adult body. The restricted expression patterns of FGFR1 isoforms, together with differential expression and binding of specific ligands, leads to activation of common FGFR1 signal transduction pathways, but may result in distinctively different biological responses as a result of differences in cellular context. FGFR1 isoforms are also present in the nucleus in complex with various fibroblast growth factors where they function to regulate transcription of target genes.

FGFR is probably activated by NCAM very differently from the way by which it is activated by FGFs, reflecting the different conditions for NCAM-FGFR and FGF-FGFR interactions. The affinity of FGF for FGFR is approximately 10e6 times higher than that of NCAM for FGFR. Moreover, in the brain NCAM is constantly present on the cell surface at a much higher (micromolar) concentration than FGFs, which only appear transiently in the extracellular environment in the nanomolar range.

Literature References
PubMed ID Title Journal Year
12791257 Structural basis for a direct interaction between FGFR1 and NCAM and evidence for a regulatory role of ATP

Kiselyov, VV, Skladchikova, G, Hinsby, AM, Jensen, PH, Kulahin, N, Soroka, V, Pedersen, N, Tsetlin, V, Poulsen, FM, Berezin, V, Bock, E

Structure 2003
16597617 Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family.

Zhang, X, Ibrahimi, OA, Olsen, SK, Umemori, H, Mohammadi, M, Ornitz, DM

J Biol Chem 2006
12141425 The structure and function of vertebrate fibroblast growth factor receptor 1

Groth, C, Lardelli, M

Int J Dev Biol 2002
16045455 Structural biology of NCAM homophilic binding and activation of FGFR

Kiselyov, VV, Soroka, V, Berezin, V, Bock, E

J Neurochem 2005
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