Cosuppression of Sprouty and Sprouty-Related Negative Regulators of FGF Signalling in Prostate Cancer: A Working Hypothesis

Figure 1

A stepwise overview of the mechanisms of sprouty and SPRED negative regulation of FGF signalling. Activation of the tyrosine kinase receptor (FGFR) results in (1) phosphorylation of Ras and subsequent activation of the MAPK signalling cascade (blue arrows); (2) FGFR activation also results in the direct activation by of Sprys by phosphorylation and increased expression via Ras-MAPK pathway (see inset: western blot of increased SPRY2 following FGF1 (10 ng·mL⁻¹) treatment of normal prostate epithelial cells); subsequent sequestration of the FGFR signalling molecule Grb (3) by pSPRY results in (4) suppression of FGF signalling. Similarly, activation of FGFR results in Spred heterodimerisation and subsequent complexing with Raf (5) resulting in inhibition of MEK activation (6).