Protein kinase C activity, phosphate uptake and endogenous substrate phosphorylation are altered in Zellweger...

Protein kinase C (PKC) is a key enzyme in lipid-mediated signal transduction. Regulation of PKC activation is dependent upon the phospholipid constituents of cellular membranes. PKC is also activated by very long-chain and long-chain cis-unsaturated fatty acids. The present study was undertaken as a first step towards elucidating a possible role for PKC in the pathogenesis of Zellweger syndrome, in which there are both perturbation of plasma membrane phospholipids and accumulation of very long-chain fatty acids. PKC activity, phosphate uptake and endogenous substrate phosphorylation were examined in intact human skin fibroblasts from Zellweger patients. PKC catalytic activity was increased in the membranous fraction of Zellweger cells compared with control cells, with no apparent translocation of the enzyme from the cytosolic to the membranous compartment. Phosphate uptake was increased in both cytosolic and membranous fractions 2.5-fold and 4.5-fold, respectively. Several proteins were extensively phosphorylated in Zellweger cells compared with control cells. These findings indicate that PKC activity is perturbed in Zellweger cells, but the exact role of PKC in altered phosphate uptake and protein phosphorylation and its relevance to the pathogenesis of Zellweger syndrome require further study.