Signaling from Fibroblast Growth Factor Receptors in Development and Disease

TLDR: Fibroblast growth factor receptors constitute a family of four structurally related, cell surface receptor tyrosine kinases (RTKs), with 55–72% homology, and are essential for embryonic and neural development, skeletal and organ formation, and adult tissue homoeostasis.

Abstract: Publisher Summary Fibroblast growth factor receptors (FGFRs) constitute a family of four (FGFR1–4) structurally related, cell surface receptor tyrosine kinases (RTKs), with 55–72% homology. FGFRs are involved in a variety of biological processes, including cell growth, migration, differentiation, survival, and apoptosis, and are essential for embryonic and neural development, skeletal and organ formation, and adult tissue homoeostasis. The three main signaling pathways associated with FGFR activation include the Ras/MAPK, PI 3-kinase, and PLCg pathways. All but one of the mutations known for the Fgfr genes are gain-of-function mutations, and activation of these receptors is associated with many developmental and skeletal disorders. Additionally, FGFR and FGF overexpression has been observed in many tumor samples, and mutations are also likely to be involved in carcinogenesis. Also, during embryonic development, FGFR signaling is essential for organ growth and patterning of the embryo. Activation of FGFRs can result in a variety of outcomes by initiating various intracellular signaling pathways. In many cases, the pathways activated depend on the cell type or stage of differentiation, leading to specific activation of downstream targets. Specific mutations in the Fgfr1–3 genes lead to congenital bone diseases classified as chondrodysplasia and craniosynostosis syndromes, which cause dwarfism, deafness, and abnormalities of the skeleton, skin, and eye. Finally, FGFRs and many of their ligands play roles in cancer progression by angiogenesis, changes in cell morphology, increased motility, and tumor cell proliferation.