Acid sensing in renal epithelial cells

Abstract

The kidney adjusts net acid excretion to match production with exquisite precision, despite little or no change in the plasma bicarbonate concentration. The acid-sensing pathway that signals the kidney to increase acid secretion involves activation of the proto-oncogene c-Src. A new study in this issue shows that proline-rich tyrosine kinase 2 (Pyk2) is responsible for acid-induced activation of c-Src and is essential for acid sensing in renal epithelial cells. The findings implicate a broader role for Pyk2 in acid-base homeostasis in bone and other tissues beyond the kidney.

Figure 1

Acid-sensing pathway in renal proximal tubular cells. A drop in extracellular fluid pH induces a corresponding decrease in intracellular pH that induces activation of Pyk2, through an unidentified mechanism, by phosphorylation on tyrosine 402. Phosphorylated Pyk2 binds to the SH2 domain of c-Src, phosphorylating and activating it, producing subsequent activation of the MAPK and JNK signaling pathways and an increase in transcription of NHE3, the sodium-hydrogen exchanger of the proximal tubule brush border.