Redistribution and Enhanced Protein Kinase C-mediated Phosphorylation of a- and y-Adducin during Renal Tumor Progression1

Tumor promotion/progression is known to be due in part to increased signaling through a variety of mitogenic pathways, including protein kinase C (PKC). To determine whether increased PKC activity could play a role in promotion and progression of renal cancer, we monitored PKC activity in normal and progressively transformed renal neoplasiasfrom Eker rats. Eker rats carry a defect in the tumor suppressor TSC2 gene that predisposes them to renal carcinoma, whereas additional factors influence tumor promotion! progression in accordance with a "two-hit" model. We used the phosphorylationof adducins at Ser-660, a known PKC phosphorylationsite, as a reporter for endogenous PKC activity. In normal proximal tubules, total adducin levels (measured with a phosphorylation state-insensitive antibody) were relatively high, whereas pSer66O-adducin(measured with a