cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic β-cells

Gomez, E. and Pritchard, C. and Herbert, Terence (2002) cAMP-dependent protein kinase and Ca2+ influx through L-type voltage-gated calcium channels mediate Raf-independent activation of extracellular regulated kinase in response to glucagon-like peptide-1 in pancreatic β-cells. Journal of Biological Chemistry, 277 (50). pp. 48146-48151. ISSN 0021-9258

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Item Type:Article
Item Status:Live Archive

Abstract

Glucagon like peptide-1 (GLP1) is a Gs-coupled receptor agonist that exerts multiple effects on pancreatic β-cells, including the stimulation of insulin gene expression and secretion. In this report, we show that treatment of the mouse pancreatic β-cell line MIN6 with GLP1 leads to the glucose-dependent activation of Erk. These effects are mimicked by forskolin, a direct activator of adenylate cyclase, and blocked by H89, an inhibitor of cAMP-dependent protein kinase. Additionally, we provide evidence that GLP1-stimulated activation of Erk requires an influx of calcium through L-type voltage-gated calcium channels and the activation of calcium/calmodulin-dependent protein kinase II. GLP1-stimulated activation of Erk is blocked by inhibitors of MEK, but GLP1 does not induce the activation of A-Raf, B-Raf, C-Raf, or Ras. Additionally, dominant negative forms of Ras(N17) and Rap1(N17) fail to block GLP1-stimulated activation of Erk. In conclusion, our results indicate that, in the presence of stimulatory concentrations of glucose, GLP1 stimulates the activation of Erk through a mechanism dependent on MEK but independent of both Raf and Ras. This requires 1) the activation of cAMP-dependent protein kinase, 2) an influx of extracellular Ca2+ through L-type voltage-gated calcium channels, and 3) the activation of CaM kinase II.

Additional Information:cited By 113 The final published version of this article can be accessed online at http://www.jbc.org/content/277/50/48146?ijkey=a93765e2f83a28dd6af19dc83380005aa29721e6&keytype2=tf_ipsecsha
Keywords:protein kinase
Subjects:B Subjects allied to Medicine > B200 Pharmacology, Toxicology and Pharmacy
Divisions:College of Science > School of Pharmacy
ID Code:28234
Deposited On:23 Aug 2018 13:33

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