Inhibition of the phosphorylation of a myristoylated alanine-rich C kinase substrate by methyl methanesulfonate in cultured NIH 3T3 cells.

The effect of methyl methanesulfonate (MMS) on the phosphorylation of an acidic 80-kDa myristoylated alanine-rich C kinase substrate (MARCKS) protein was investigated in NIH 3T3 fibroblasts. An alkylating agent, MMS inhibited protein kinase C activity and the phosphorylation of MARCKS. MMS treatment also lowered the cellular amounts of second messengers of inositol-1,4,5-trisphosphate and diacylglycerol. Data suggest that MMS decreased the phosphorylation of phospholipase C, a protein whose activity is influenced by its phosphorylation state. We present here the first report that MMS intervenes in a signal cascade by inhibiting the phosphorylation of phospholipase C, which in turn leads to the inactivation of protein kinase C and the subsequent inhibition of MARCKS phosphorylation.