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Signalling pathway leading to an activation of mitogen-activated protein kinase by stimulating M3 muscarinic receptor.

Kim, JY; Yang, MS; Oh, CD; Kim, KT; Ha, MJ; Kang, SS; Chun, JS
The Biochemical journal, 337(Pt2):275-280, 1999
Journal Title
The Biochemical journal
The signalling pathway leading to an activation of mitogen-activated protein (MAP) kinase subtypes Erk-1 and -2 upon stimulation of muscarinic receptor with carbachol in human neuroblastoma SK-N-BE2(C) cells was investigated. Carbachol activated Erk-1/-2 by stimulating M3 muscarinic receptor, as determined by specific antagonists for individual muscarinic receptors. The activation of Erk-1/-2 by carbachol was blocked by the inhibition or down-regulation of protein kinase C (PKC). Among the multiple PKC isoforms expressed in SK-N-BE2(C) cells, only PKCepsilon was activated by the treatment of carbachol, and selective down-regulation of PKCepsilon was sufficient to block Erk-1/-2 activation. Carbachol treatment induced activation of the serine/threonine protein kinase Raf, and an inhibition of Raf blocked Erk-1/-2 activation. Ectopic expression of inhibitory small GTPase Ras, RasN17, blocked the carbachol-induced Raf activation without affecting the activation of PKCepsilon, while the inhibition of PKC blocked the Raf activation. Thus, these results suggest that carbachol-induced activation of PKCepsilon mediates Erk-1/-2 activation by a sequential activation of Ras, Raf and MAP kinase kinase.
MeSH terms
Calcium-Calmodulin-Dependent Protein Kinases/metabolism*Carbachol/pharmacologyEnzyme ActivationHumansIsoenzymes/metabolism*Mitogen-Activated Protein Kinase 1/metabolismMitogen-Activated Protein Kinase 3Mitogen-Activated Protein Kinases*Protein Kinase C/metabolism*Protein Kinase C-epsilonProto-Oncogene Proteins c-raf/metabolismProto-Oncogene Proteins p21(ras)/metabolismReceptor, Muscarinic M3Receptors, Muscarinic/metabolism*Signal TransductionTumor Cells, Cultured
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Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
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하, 만준
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