Ciprofibrate stimulates protein kinase C-dependent phosphorylation of an 85 kDa protein in rat Fao hepatic derived cells.
The effect of ciprofibrate on early events of signal transduction was previously studied in Fao cells. Protein kinase C (PKC) assays performed on permeabilized cells showed a more than two-fold increase in PKC activity in cells treated for 24 h with 500 microM ciprofibrate. To show the subsequent effect of this increase on protein phosphorylation, the in vitro phosphorylation on particulate fractions obtained from Fao cells was studied. Among several modifications, the phosphorylation of protein(s) with an apparent molecular mass of 85 kDa was investigated. This modification appeared in the first 24 h of treatment with 500 microM ciprofibrate. It was shown to occur on Ser/Thr residue(s). It was calcium but not calmodulin-dependent. The phosphorylation level of this/these protein(s) was reduced with kinase inhibitors and especially with 300 nM GF-109203X, a specific inhibitor of PKC. All these results suggest that the phosphorylation of the 85 kDa protein(s) is due to a PKC or to another Ser/Thr kinase activated via a PKC pathway. A possible biochemical candidate for 85 kDa protein seems to be the beta isoform of phosphatidylinositol 3-kinase regulatory subunit.
Passilly-Degrace
P
P
Laboratoire de Biologie Moléculaire et Cellulaire, Université de Bourgogne, Faculté des Sciences Gabriel, 6, boulevard Gabriel, 21000, Dijon, France.
Jannin
B
B
Boscoboinik
D
D
Motojima
K
K
Latruffe
N
N
D000818:Animals; D002460:Cell Line; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D058607:Fibric Acids; D008099:Liver / Q000378:metabolism*; D008970:Molecular Weight; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012694:Serine; D013379:Substrate Specificity; D013912:Threonine
D058607:Fibric Acids; D020025:Peroxisome Proliferators; D010750:Phosphoproteins; D013912:Threonine; D012694:Serine; D002995:Clofibric Acid; D011493:Protein Kinase C; C019304:ciprofibrate