Analysis of the Signaling Pathway Involved in the Regulation of Hexokinase II Gene Transcription by Insulin
| Autor: | Daryl K. Granner, Haruhiko Osawa, Calum Sutherland, Richard L. Printz, R. Brooks Robey |
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| Rok vydání: | 1996 |
| Předmět: |
Monosaccharide Transport Proteins
Transcription Genetic medicine.medical_treatment Muscle Proteins P70-S6 Kinase 1 Polyenes Biochemistry Cell Line Wortmannin Insulin Antagonists chemistry.chemical_compound Hexokinase medicine Animals Insulin RNA Messenger Enzyme Inhibitors Muscle Skeletal Protein kinase A Molecular Biology Flavonoids Sirolimus Glucose Transporter Type 4 biology Myocardium Glucose transporter Cell Biology Molecular biology Rats Androstadienes Insulin receptor Adipose Tissue chemistry biology.protein Signal transduction Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 271:16690-16694 |
| ISSN: | 0021-9258 |
| Popis: | The hexokinases, by converting glucose to glucose 6-phosphate, help maintain the glucose concentration gradient that results in the movement of glucose into cells through the facilitative glucose transporters. Hexokinase II (HKII) is the major hexokinase isoform in skeletal muscle, heart, and adipose tissue. Insulin induces HKII gene transcription in L6 myotubes, and this, in turn, increases HKII mRNA and the rates of HKII protein synthesis and glucose phosphorylation in these cells. Inhibitors of distinct insulin signaling pathways were used to dissect the molecular mechanism by which HKII gene expression is induced by insulin in L6 myotubes. Treatment with wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), or with rapamycin, an inhibitor of the pathway from the insulin receptor to p70/p85 ribosomal S6 protein kinase (p70(s6k)), prevented the induction of HKII mRNA by insulin. In contrast, treatment with PD98059, an inhibitor of mitogen-activated protein kinase activation, had no effect on insulin-induced HKII mRNA. In addition, rapamycin blocked the insulin-induced expression of an HKII promoter-chloramphenicol acetyltransferase fusion gene transiently transfected into L6 myotubes, whereas PD98059 had no such effect. These results suggest that a phosphatidylinositol 3-kinase/p70(s6k)-dependent pathway is required for regulation of HKII gene transcription by insulin and that the Ras-mitogen-activated protein kinase-dependent pathway is probably not involved. |
| Databáze: | OpenAIRE |
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