Reduced protein kinase C activity in a ras-resistant cell line derived from Ki-MSV transformed cells

Abstract

We have examined phosphatidylinositol turnover and C-kinase distribution in a flat cellular ras-resistant cell line (C11) derived from Kirsten murine sarcoma virus (Ki-MSV) transformed NIH/3T3 cells (DT). This cell type has been shown to express high levels of the p21 Ki-ras gene product yet is resistant to the transforming effects of this protein. Our data indicate that C11 cells have reduced levels of total C-kinase activity when compared to NIH/3T3 cells and do not retain the ability to phosphorylate the growth associated 80-kDa C-kinase substrate either in vivo or in vitro. Furthermore, whilst the steady state levels of diacylglycerol and the sum of inositol phosphates are elevated in DT cells, in C11 cells these levels are reduced to an amount equivalent to that seen in NIH/3T3 cells. These data indicate a correlation between a protein kinase C dependent pathway and resistance to transformation by ras.