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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.
Authors
Stephen L. Gluck
Figure 1
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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.
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ISSN: 0021-9738 (print), 1558-8238 (online)