description
Signaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that become tyrosine phosphorylated in response to FGF-stimulation and form a complex with additional complement of signaling proteins. The activation loop in the catalytic domain of FGFR maintains the PTK domain in an inactive or low activity state. The activation-loop of FGFR1, for instance, contains two tyrosine residues that must be autophosphorylated for maintaining the catalytic domain in an active state. In the autoinhibited configuration, a kinase invariant proline residue at the C-terminal end of the activation loop interferes with substrate binding while allowing access to ATP in the nucleotide binding site.In addition to the catalytic PTK core, the cytoplasmic domain of FGFR contains several regulatory sequences. The juxtamembrane domain of FGFRs is considerably longer than that of other receptor tyrosine kinases. This region contains a highly conserved sequence that serves as a binding site for the phosphotyrosine binding (PTB) domain of FRS2. A variety of signaling proteins are phosphorylated in response to FGF stimulation, including Shc, phospholipase-C gamma and FRS2 leading to stimulation of intracellular signaling pathways that control cell proliferation, cell differentiation, cell migration, cell survival and cell shape

external resources
NCBI:1269422
REACTOME:R-HSA-5654716
PUBMED:8752212

genes
FGF1 , FGF2 , FGF4 , FGF6 , FGF8 , FGF9 , FGFR4 , GAB1 , GRB2 , HRAS , KRAS , NRAS , PIK3CA , PIK3R1 , PLCG1 , PTPN11 , SHC1 , SOS1 , FGF23 , FGF18 , FGF17 , FGF16 , FGF19 , FRS3 , FRS2 , FGF20 , KLB ,