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. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company