Figure 7. The working hypothesis regarding the putative pathophysiological link between cavernous liver hemangioma and autosomal dominant polycystic kidney disease. Blocking of calcium egress from the endoplasmic reticulum by defective polycystin-2 leads to ERK1/2 activation via the AC6-cyclic AMP/protein kinase A pathway, and by means of hypoxia-inducible-factor-1α mediation, to vascular endothelial growth factor (VEGF) secretion and autocrine and paracrine stimulation of VEGFR-2. VEGFR-2 activation results in activation of the RAS/RAF/MEK/ERK1/2 pathway, which induces proliferation of cells in the tubular epithelium, cholangiocytes, and endothelium. The result is generation of cysts in the kidney and cysts and hemangiomas in the liver.