Differential regulation of mRNAs encoding three protein-tyrosine phosphatases by insulin and activation of protein kinase C.
Protein-tyrosine phosphatases (PTPases) play an essential role in the control of signalling through phosphotyrosine pathways. Since little is known about the regulation of these enzymes, we examined the effect of insulin and phorbol 12-myristate 13-acetate (PMA) treatment of well-differentiated rat hepatoma (Fao) cells on the expression of mRNAs encoding three major PTPase homologs in liver: PTPase1B, an intracellular enzyme with a single conserved PTPase domain, and two tandem-domain, transmembrane PTPases, known as LAR and LRP. Treatment of serum-deprived cells with 100 nM insulin increased the abundance of the 4.3 kb and 1.6 kb mRNAs encoding PTPase1B on Northern analysis by 1.6 and 3.1-fold, respectively (p < or = 0.02). Similarly, exposure to 100 ng/ml PMA increased the 4.3 and 1.6 kb PTPase1B mRNAs by 4.5 and 5.7-fold, respectively (p < or = 0.035). In contrast, treatment with insulin or PMA had no significant effect of the abundance of mRNA encoding either LAR or LRP. PMA appeared to have a transcriptional effect on the PTPase1B gene by a protein kinase C-mediated mechanism. The increase in PTPase1B mRNA expression by insulin and PMA suggests that this PTPase may provide feed-back regulation of signalling through the insulin action pathway as well as a potential link between the action of protein kinase C and the regulation of specific phosphotyrosine residues in cells.
D000818:Animals; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004789:Enzyme Activation; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology*; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D016895:Culture Media, Serum-Free; D007328:Insulin; D012333:RNA, Messenger; D019000:Phosphotyrosine; D014443:Tyrosine; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases; D013755:Tetradecanoylphorbol Acetate