| Developmental and Signaling Pathways: Schematic model of the FGF signalling cascade |
| Muha, V. and Muller, H. A. (2013). Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster. Int J Mol Sci 14: 5920-5937. PubMed ID: 23493057 |
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Legend: Schematic model of the FGF signalling cascade FGFs bind to their FGFRs and this interaction is stabilized by heparan sulfate proteoglycans (HSPG). Activation of the FGFR leads to auto- and trans-phosphorylation of their tyrosine kinase domains and to phosphorylation of its adaptor protein Dof. Dof protein is O-GlcNAcylated (O-GlcNAc) and possesses multiple clusters of tyrosine residues directing the signal towards various cascades, three of which—the Csw/Shp2, Grb2/Drk and Src64B pathways—have been proposed to contribute to MAPK activation. This route of FGF signalling is responsible for inducing gene transcription, and executing proliferative and anti-apoptotic responses. Dof also contains a putative binding site for PI3K that could locally modify the phosphatidylinositol (PtdIns) composition of the plasma membrane and thus recruit downstream signalling components for example the RhoGEF Pbl. Pbl acts on the Rac pathway to promote the formation of actin rich protrusions in the mesoderm. Actin polymerisation is required for protrusion formation in a Rac-, Cdc42- and FGF-dependent fashion. Putative interactions are indicated as grey arrows and the putative component of the Drosophila FGF pathway, PI3K, is represented as a circle with no border. (Muha, 2013). |
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