1. PIcKing on Fibroblast Growth Factor Receptors as Bladder Cancer Therapeutic Targets 
Miriam Marqués, Francisco X. Real 
European Urology 
Volume 71, Issue 6, Pages (June 2017)
DOI: /j.eururo
Copyright © 2017 European Association of Urology Terms and Conditions

2. Fig. 1
Signal transduction by fibroblast growth factor receptors (FGFRs) and feedback mechanisms. Ligand-mediated receptor dimerization induces FGFR intrinsic kinase activity. Signaling pathways activated by FGFRs are shown in green. Once activated, FGFRs phosphorylate and activate PLCγ, generating DAG and IP3, which in turn induces intracellular Ca2+ release and PKC activation. The other major downstream signaling branch activated by FGFRs depends on the docking protein FRS2. Activated FGFRs phosphorylate FRS2, which recruits GRB2 and SHP2. GRB2 in turn recruits PI3K through GAB1 and activates RAS through the nucleotide exchange factor SOS. The tyrosine-kinase PYK2 is also activated by FGFRs. Molecular effectors of FGFR signaling are shown in yellow. Downstream of ERK, RSK2 is a key direct effector of survival and transformation. AKT and ERK phosphorylate the TSC1/TSC2 complex, cooperating in mTORC1 activation. STAT proteins mediate cellular responses downstream of FGFRs. Feedback mechanisms activated by FGFRs are shown in red. In response to FGFs, the ubiquitin ligase c-CBL mediates FGFR monoubiquitination, targeting it for lysosomal degradation. SPRYs and the MKPs/DUSPs provide MAPK negative feedback regulation. MAPK itself phosphorylates FRS2 and tempers FGFR signal transduction. AKT also mediates inhibitory mechanisms subsequent to FGFR activation. Red asterisks denote genes frequently mutated in BC. DAG=diacylglycerol; IP3=inositol triphosphate.
European Urology  , DOI: ( /j.eururo )
Copyright © 2017 European Association of Urology Terms and Conditions