Fig. 9. A schematic drawing of the Src-dependent anti-apoptotic mechanisms of serum-independent proliferation in 5637 bladder carcinoma cells.
Cells recognize or sense the signal of serum-starved conditions by unknown mechanism and then promote the activation of Src. Gene expression and secretion of HB-EGF is stimulated in a Src and MMP-dependent manner. HB-EGF, as a ligand, activates EGFR. The activated EGFR, in corporation with Src, contributes to the tyrosine phosphorylation of p145met. UPIIIa, a newly characterized protein in this study, undergoes partial proteolysis in an MMP (and maybe Src)-dependent manner under serum-starved conditions, by which it contributes to the activation of Src. Cholesterol-enriched MDs, as indicated by the grey area on the plasma membranes, serve as a platform for the signaling network as described above. For detail, see Discussion.