Expression of ras oncogene leads to down-regulation of protein kinase C.
The effect of mutated c-Ha-ras expression on Ca2+ and phospholipid-dependent protein kinase C (PKC) activity during the process of transformation was analysed using an inducible metallothionein-ras hybrid oncogene system. A close correlation was found between the timing of ras expression and the loss of PKC enzymatic activity measured in a cell-free system. Examination of the subcellular distribution of the enzyme in inducible and constitutive ras-transformants revealed that expression of ras was associated with an apparent translocation of PKC to the plasma membrane concomitant with down-regulation of PKC enzymatic activity in particulate as well as cytosolic fractions. Quantitation of PKC protein utilizing a PKC-specific antiserum showed that ras expression was associated with a decrease in the total amount of PKC protein present in the cell. We conclude that transformation by c-Ha-ras is accompanied by down-regulation of PKC activity and that the basis of this effect may, to a large extent, lie in the down-regulation of the amount of PKC protein.
Mount Sinai Hospital Research Institute, University of Toronto, Ontario, Canada.
T
T
Haliotis
W
W
Trimble
S
S
Chow
S
S
Bull
G
G
Mills
P
P
Girard
J F
JF
Kuo
N
N
Hozumi
D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000201:enzymology; D002474:Cell-Free System / Q000201:enzymology; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008809:Mice, Inbred C3H; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D014170:Transformation, Genetic / Q000235:genetics / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000201:enzymology
D011493:Protein Kinase C