Reactome | Signaling by FGFR1

Signaling by FGFR1

Stable Identifier

R-HSA-5654736

DOI

10.3180/R-HSA-5654736.3

Type

Pathway

Species

Homo sapiens

Synonyms

Fibroblast Growth Factor Receptor (FGFR) signaling

ReviewStatus

5/5

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The 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosine kinases (RTKs) designated FGFR1, FGFR2, FGFR3 and FGFR4. These receptors are key regulators of several developmental processes in which cell fate and differentiation to various tissue lineages are determined. Unlike other growth factors, FGFs act in concert with heparin or heparan sulfate proteoglycan (HSPG) to activate FGFRs and to induce the pleiotropic responses that lead to the variety of cellular responses induced by this large family of growth factors. An alternative, FGF-independent, source of FGFR activation originates from the interaction with cell adhesion molecules, typically in the context of interactions on neural cell membranes and is crucial for neuronal survival and development.

Upon ligand binding, receptor dimers are formed and their intrinsic tyrosine kinase is activated causing phosphorylation of multiple tyrosine residues on the receptors. These then serve as docking sites for the recruitment of SH2 (src homology-2) or PTB (phosphotyrosine binding) domains of adaptors, docking proteins or signaling enzymes. Signaling complexes are assembled and recruited to the active receptors resulting in a cascade of phosphorylation events.

This leads to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape, depending on the cell type or stage of maturation.

Literature References

PubMed ID	Title	Journal	Year
19247306	The FGF family: biology, pathophysiology and therapy Beenken, A, Mohammadi, M	Nat Rev Drug Discov	2009
15863038	Mechanisms underlying differential responses to FGF signaling Ambrosetti, D, Basilico, C, Mansukhani, A, Dailey, L	Cytokine Growth Factor Rev	2005
15567848	Common and distinct elements in cellular signaling via EGF and FGF receptors Schlessinger, J	Science	2004
12080084	FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease Ornitz, DM, Marie, PJ	Genes Dev	2002
16597617	Receptor specificity of the fibroblast growth factor family. The complete mammalian FGF family. Ornitz, DM, Umemori, H, Mohammadi, M, Olsen, SK, Ibrahimi, OA, Zhang, X	J Biol Chem	2006
7917292	Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin Williams, EJ, Walsh, FS, Furness, J, Doherty, P	Neuron	1994
20602996	Cell signaling by receptor tyrosine kinases Schlessinger, J, Lemmon, MA	Cell	2010
15863030	Cellular signaling by fibroblast growth factor receptors Schlessinger, J, Eswarakumar, VP, Lax, I	Cytokine Growth Factor Rev	2005