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.
Shin
I
I
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejon, South Korea.
Kam
Y
Y
Ha
K S
KS
Kang
K W
KW
Joe
C O
CO
D016475:3T3 Cells; D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D051379:Mice; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004075:Diglycerides; D004791:Enzyme Inhibitors; D007295:Inositol Phosphates; D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D011506:Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D008741:Methyl Methanesulfonate; D011493:Protein Kinase C; D010738:Type C Phospholipases