Blockade of rapid versus prolonged extracellularly regulated kinase 1/2 activation has differential effects on insulin-induced gene expression.
In the present work, insulin's regulation of expression of activating transcription factor 3 (ATF-3), the putative transcription factor proline-rich induced protein (Pip)92, and insulin-inducible gene-1 (Insig-1) (an ER resident protein involved in regulation of sterol-responsive element-binding protein 1 activation) have been examined in a liver-derived cell line (rat H4IIE hepatoma cells). We report that: 1) insulin-induced transcription of ATF-3, Pip92, and Insig-1 required MEK-ERK activation; 2) insulin-induced transcription of ATF-3 and Pip92 reached maximum levels within 15 min and was blocked by wortmannin but not LY294002; 3) in contrast, the maximum level of insulin-induced transcription of Insig-1 was delayed and was not blocked by either wortmannin or LY294002; 4) insulin activated ERK1/2 in two distinct phases, a rapid peak and a later plateau; 5) the delayed plateau phase of insulin-induced ERK1/2 activation was partially phosphatidylinositol 3-OH-kinase dependent; and 6) however, the rapid, insulin-induced peak of ERK1/2 activation was blocked by wortmannin but not LY294002.
Keeton
Adam B
AB
Department of Pathology, Division of Molecular and Cellular Pathology, Volker Hall, G019, 1670 University Boulevard, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
Bortoff
Katherine D
KD
Franklin
J Lee
JL
Messina
Joseph L
JL
D051700:Activating Transcription Factor 3; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins; D008113:Liver Neoplasms; D008565:Membrane Proteins / Q000235:genetics; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D000077191:Wortmannin
D051700:Activating Transcription Factor 3; D000730:Androstadienes; C497108:Atf3 protein, rat; D002867:Chromones; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; C491574:Insig1 protein, rat; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D011506:Proteins; D014157:Transcription Factors; C484022:pip92 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077191:Wortmannin