Protein kinase C in mouse kidney: effect of the Hyp mutation and phosphate deprivation.

Abstract

To test whether protein kinase C plays a role in the regulation of renal brush border membrane phosphate transport and mitochondrial vitamin D metabolism, we examined the activity, distribution and endogenous substrates of protein kinase C in renal subcellular fractions derived from two mouse models exhibiting perturbations in both renal functions. The X-linked Hyp mouse is characterized by reduced phosphate transport and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis relative to normal, whereas the phosphate-deprived mouse exhibits elevated phosphate transport and vitamin D hormone synthesis. Protein kinase C activity was higher in renal cytosol of Hyp mice, when compared to normal littermates (358 +/- 11 vs. 244 +/- 31 pmol 32P/mg prot/min, P less than 0.02), whereas genotype differences in brush border membrane and mitochondrial kinase were not apparent. Phosphate deprivation of normal mice elicited a 50% reduction in brush border membrane protein kinase C (from 819 +/- 56 to 460 +/- 48 pmol 32P/mg prot/min, P less than 0.03), an increase in mitochondrial kinase (from 57 +/- 7 to 87 +/- 10 pmol 32P/mg prot/min, P less than 0.03), and no change in cytosolic kinase activity. Phosphate deprivation of Hyp mice led to an increase in mitochondrial protein kinase C (from 72 +/- 7 to 98 +/- 9 pmol 32P/mg prot/min, P less than 0.03) and no change in either brush border membrane or cytosolic kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)