期刊
JOURNAL OF LIPID RESEARCH
卷 56, 期 4, 页码 859-870出版社
ELSEVIER
DOI: 10.1194/jlr.M056051
关键词
protein kinase C zeta; lyso-phosphatidylcholine; caveolin-1-containing endocytic vesicle; chylomicrons
资金
- Veterans Administration
Chylomicron output by the intestine is proportional to intestinal phosphatidylcholine (PC) delivery. Using five different variations of PC delivery to the intestine, we found that lyso-phosphatidylcholine (lyso-PC), the absorbed form of PC, concentrations in the cytosol (0 to 0.45 nM) were proportional to the input rate. The activity of protein kinase C (PKC)zeta, which controls prechylomicron output rate by the endoplasmic reticulum (ER), correlated with the lyso-PC concentration suggesting that it may be a PKC zeta activator. Using recombinant PKC zeta, the K-m for lyso-PC activation was 1.49 nM and the V-max 1.12 nM, more than the maximal lyso-PC concentration in cytosol, 0.45 nM. Among the phospholipids and their lyso derivatives, lyso-PC was the most potent activator of PKC zeta and the only one whose cytosolic concentration suggested that it could be a physiological activator because other phospholipid concentrations were negligible. PKC zeta was on the surface of the dietary fatty acid transport vesicle, the caveolin-1-containing endocytic vesicle. Once activated, PKC zeta, eluted off the vesicle. A conformational change in PKC zeta on activation was suggested by limited proteolysis. We conclude that PKC zeta on activation changes its conformation resulting in elution from its vesicle. The downstream effect of dietary PC is to activate PKC zeta, resulting in greater chylomicron output by the ER.
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