Cellular signaling by fibroblast growth factor receptors.

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Eswarakumar VP, Lax I, Schlessinger J

Cellular signaling by fibroblast growth factor receptors.

Cytokine Growth Factor Rev. 2005 Apr;16(2):139-49. Epub 2005 Feb 1.

PubMed ID
15863030 [ View in PubMed
]
Abstract

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. 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. A variety of human skeletal dysplasias have been linked to specific point mutations in FGFR1, FGFR2 and FGFR3 leading to severe impairment in cranial, digital and skeletal development. Gain of function mutations in FGFRs were also identified in a variety of human cancers such as myeloproliferative syndromes, lymphomas, prostate and breast cancers as well as other malignant diseases. The binding of FGF and HSPG to the extracellular ligand domain of FGFR induces receptor dimerization, activation and autophosphorylation of multiple tyrosine residues in the cytoplasmic domain of the receptor molecule. A variety of signaling proteins are phosphorylated in response to FGF stimulation including Shc, phospholipase-Cgamma, STAT1, Gab1 and FRS2alpha leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape. The docking proteins FRS2alpha and FRS2beta are major mediators of the Ras/MAPK and PI-3 kinase/Akt signaling pathways as well as negative feedback mechanisms that fine-tune the signal that is initiated at the cell surface following FGFR stimulation.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Fibroblast growth factor 1P05230Details
Fibroblast growth factor receptor 2P21802Details
Phosphatidylinositol 3-kinase regulatory subunit alphaP27986Details
Fibroblast growth factor 2P09038Details
Fibroblast growth factor receptor 4P22455Details
Fibroblast growth factor receptor 1P11362Details
Fibroblast growth factor receptor 3P22607Details