Figure 2. Network of pathways and transcription functions that regulate cell cycle progression, energy metabolism, and cell proliferation and death that are abnormal in PKD.

Upregulation of B-Raf/Mek/ERK, PI3K/AKT, and Wnt/β-catenin pathways and MYC and HIF transcription factors and downregulation of the LKB1/AMPK/TSC pathway, GSK3, and p53 promote aerobic glycolysis and cell cycle progression. Upregulation of MYC and downregulation of p53 exert proapoptotic and antiapoptotic effects, respectively. Downregulation of AMPK stimulates ion transport and fluid secretion. At multiple levels in this network, PKA activity stimulates proproliferative and inhibits antiproliferative signals. Yellow indicates proteins that are reduced in PKD; blue indicates proteins that are increased in PKD. OXPHOS, oxidative phosphorylation.