Figure 3.

Model of Src downregulation of von Hippel–Lindau (VHL) tumor suppressor protein and promotion of tumor angiogenesis and tumor progression. Src-directed posttranslational tyrosine phosphorylation modification of VHL allows tagging and recruitment of VHL for proteolysis by an E3 ligase complex. Also, posttranslational modification of VHL may displace VHL from the VHL E3 ligase complex (thereby facilitating ubiquitin tagging and recruitment of VHL for proteolysis by E3 ligase complexes and/or facilitating VHL protein instability). Consequently, increased levels of HIF-1α upregulate vascular endothelial growth factor (VEGF) production and ultimately increase tumor angiogenesis and the potential for tumor progression.