Activation of MAP kinase by MC4-R through PI3 kinase.
The melanocortin 4 receptor (MC4-R) is a Galpha s-coupled receptor known to increase cAMP production following agonist stimulation. We demonstrate that the mitogen-activated protein kinases p42 (ERK2) and p44 (ERK1) are also activated by MC4-R following treatment with the MC4-R agonist NDP-alpha-MSH in stably transfected CHO-K1 cells. This time- and dose-dependent response is abolished by the MC4-R antagonist SHU-9119. p42/p44 MAPK activation is blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002 but not by the protein kinase A (PKA) inhibitor Rp-cAMPS, indicating that that signal activating the p42/p44 MAPK pathway is conveyed through inositol triphosphate.
Vongs
Aurawan
A
Department of Metabolic Research-Obesity, Merck Research Laboratories, Merck and Co., P.O. Box 2000, RY80M-213 Rahway, NJ 07065, USA.
Lynn
Nicole M
NM
Rosenblum
Charles I
CI
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000494:pharmacology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D047428:Protein Kinase Inhibitors; D044105:Receptor, Melanocortin, Type 4; C103272:SHU 9119; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D009074:Melanocyte-Stimulating Hormones; D000242:Cyclic AMP; D019869:Phosphatidylinositol 3-Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D048052:Mitogen-Activated Protein Kinase 3; D000077191:Wortmannin