Phosphorylation, protein kinases and ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by renal cyst formation and caused by mutations in the PKD1 and PKD2 genes, which encode polycystin-1(PC-1) and -2 (PC-2) proteins, respectively. PC-1 is a large plasma membrane receptor involved in the regulation of several biological functions and signaling pathways including the Wnt cascade, AP-1, PI3kinase/Akt, GSK3β, STAT6, Calcineurin/NFAT and the ERK and mTOR cascades. PC-2 is a calcium channel of the TRP family. The two proteins form a functional complex and prevent cyst formation, but the precise mechanism(s) involved remains unknown. This article is part of a Special Issue entitled: Polycystic Kidney Disease.

► Growing evidence suggests a role for polycystin-1 in phosphorylation and cell signaling.
► Polycystin-1 regulates several signaling cascades including Wnt, AP-1, PI3kinase/Akt, GSK3β, STAT6, the ERK and mTOR cascades.
► cAMP excess is involved in the pathogenesis of ADPKD.
► Protein kinase X can restore normal function to PKD1-deficient kidneys.