Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP) and glucocorticoids stimulate transcription of the PEPCK gene whereas insulin and phorbol esters have a dominant inhibitory effect. Wortmannin, an inhibitor of 1-phosphatidylinositol 3-kinase (PI 3-kinase), blocks the inhibition of glucocorticoid- and cAMP-stimulated PEPCK gene transcription by insulin. By contrast, although phorbol esters mimic the action of insulin on the regulation of PEPCK gene transcription, wortmannin does not block the effect of these agents. Thus PI 3-kinase is required for the regulation of PEPCK gene expression by insulin but not by phorbol esters. In liver cells, insulin administration stimulates the activity of multiple protein kinases, including the p42/p44 Mitogen Activated Protein (MAP) kinase and the p70/p85 ribosomal protein S6 kinase. Selective inhibition of the activation of either kinase, utilizing the compounds PD98059 and rapamycin respectively, does not affect insulin regulation of PEPCK gene transcription. Thus regulation of PEPCK gene transcription requires PI 3-kinase but does not require the activation of either p42/p44 MAP kinase or p70/p85 ribosomal protein S6 kinase.
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PMID:New connections in the regulation of PEPCK gene expression by insulin. 865 Feb 66

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the rate-limiting step in hepatic gluconeogenesis. Glucagon (via the second messenger cAMP), retinoic acid, and glucocorticoids stimulate transcription of the PEPCK gene, whereas insulin and phorbol esters have a dominant inhibitory effect. We now show that oxidative and chemical stress (hydrogen peroxide and sodium meta-arsenite, respectively) also produce a dominant inhibitory effect, both on the endogenous PEPCK gene and on a stably transfected PEPCK-chloramphenicol acetyl transferase (CAT) fusion gene. Wortmannin, an inhibitor of 1-phosphatidylinositol 3-kinase (PI 3-kinase), blocks the inhibition of glucocorticoid and cAMP-induced PEPCK gene transcription by insulin; however, it has no effect on the inhibition elicited by oxidative or chemical stress. Thus, the mechanism(s) used by hydrogen peroxide and sodium meta-arsenite to regulate PEPCK gene expression are PI 3-kinase independent. This suggests that these agents operate by a pathway distinct from that used by insulin or that the pathways converge at a point downstream of PI 3-kinase. The reactivating kinase (RK, also known as p38 mitogen activated protein kinase) is induced by insulin, hydrogen peroxide, or sodium meta-arsenite in hepatoma cells, and these effects are blocked by SB203580, a selective inhibitor of RK. However, SB203580 has no effect on the ability of any of these agents to regulate PEPCK-CAT fusion gene expression. Thus, although RK has a role in the regulation of lymphokine gene expression in monocytes, it is not required for the regulation of PEPCK expression by either insulin or oxidative and chemical stress in hepatoma cells.
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PMID:Oxidative and chemical stress mimic insulin by selectively inhibiting the expression of phosphoenolpyruvate carboxykinase in hepatoma cells. 897 Oct 75

Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the first committed step in hepatic gluconeogenesis. Glucagon and glucocorticoids stimulate PEPCK gene transcription, whereas insulin has a dominant inhibitory effect. We have shown that inhibitors of 1-phosphatidylinositol 3-kinase (PI 3-kinase) block this action of insulin. In contrast, three distinct agents, all of which prevent activation of p42/p44 mitogen-activated protein (MAP) kinase, have no effect on the regulation of PEPCK transcription by insulin. However, a subsequent report has suggested that this pathway is involved in the inhibition of cAMP-induced PEPCK gene transcription by insulin. To address these conflicting data, we re-examined the Ras MAP kinase pathway, not only with respect to regulation of PEPCK gene transcription, but also for regulation of PI 3-kinase and p42/p44 MAP kinase. Overexpression of constitutively active Ras (V61) (or Raf-1 (RafCAAX)) partially represses PEPCK transcription in hepatoma cells. However, an inhibitor of MAP kinase kinase blocks this action of RafCAAX but has no effect on regulation of PEPCK gene transcription by insulin. Second, the action of a dominant negative Ras (N17Ras) on PEPCK gene transcription correlates more closely with the inhibition of PI 3-kinase than with the inhibition of p42/p44 MAP kinase. Third, insulin cannot activate p42/p44 MAP kinase in the presence of cAMP even though cAMP-induced PEPCK gene transcription is inhibited by insulin. This data confirms that the Ras MAP kinase pathway is not required for the regulation of PEPCK gene transcription by insulin and demonstrates the importance of employing multiple techniques when investigating the function of signaling pathways.
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PMID:Activation of the ras mitogen-activated protein kinase-ribosomal protein kinase pathway is not required for the repression of phosphoenolpyruvate carboxykinase gene transcription by insulin. 945 31