Signaling by FGFR1

Stable Identifier
R-HSA-5654736
Type
Pathway
Species
Homo sapiens
Synonyms
Fibroblast Growth Factor Receptor (FGFR) signaling
Locations in the PathwayBrowser
Summation

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
15863038 Mechanisms underlying differential responses to FGF signaling

Dailey, L, Ambrosetti, D, Mansukhani, A, Basilico, C

Cytokine Growth Factor Rev 2005
19247306 The FGF family: biology, pathophysiology and therapy

Beenken, A, Mohammadi, M

Nat Rev Drug Discov 2009
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.

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

J Biol Chem 2006
7917292 Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin

Williams, EJ, Furness, J, Walsh, FS, Doherty, P

Neuron 1994
20602996 Cell signaling by receptor tyrosine kinases

Lemmon, MA, Schlessinger, J

Cell 2010
15863030 Cellular signaling by fibroblast growth factor receptors

Eswarakumar, VP, Lax, I, Schlessinger, J

Cytokine Growth Factor Rev 2005
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