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

J Y Kim1, M S Yang, C D Oh

  • 1Department of Biology, Kyungpook National University, Taegu 702-701, Korea.

The Biochemical Journal
|January 12, 1999
PubMed

Insights

Carbachol activates Erk-1/-2 via M3 muscarinic receptors, involving protein kinase C epsilon (PKCepsilon), Ras, and Raf signaling in neuroblastoma cells.

Area of Science:

  • Neuroscience
  • Cell Signaling
  • Molecular Biology

Background:

  • Mitogen-activated protein (MAP) kinases, including Erk-1 and Erk-2, are crucial in cellular processes.
  • Muscarinic receptors mediate various cellular responses.
  • Understanding signaling pathways is vital for neurobiology research.

Purpose of the Study:

  • To investigate the signaling pathway for mitogen-activated protein (MAP) kinase Erk-1/-2 activation.
  • To elucidate the role of muscarinic receptors and protein kinase C (PKC) in this pathway.
  • To identify specific PKC isoforms involved in carbachol-induced signaling.

Main Methods:

  • Utilized human neuroblastoma SK-N-BE2(C) cells.
  • Employed specific antagonists for muscarinic receptors.
  • Investigated protein kinase C (PKC) isoforms and their activation.
  • Assessed the role of Ras and Raf in the signaling cascade.
  • Used selective down-regulation and ectopic expression of signaling molecules.

Main Results:

  • Carbachol activated Erk-1/-2 through the M3 muscarinic receptor.
  • Protein kinase C epsilon (PKCepsilon) was identified as the key PKC isoform activated by carbachol.
  • PKCepsilon activation was necessary for Erk-1/-2 activation.
  • Carbachol induced Raf activation, which was downstream of PKCepsilon but upstream of MAP kinase kinase.
  • Ras activation was upstream of Raf but independent of PKCepsilon.

Conclusions:

  • Carbachol-induced Erk-1/-2 activation in neuroblastoma cells is mediated by a pathway involving M3 muscarinic receptor, PKCepsilon, Ras, and Raf.
  • PKCepsilon acts as a critical link between receptor activation and downstream MAP kinase signaling.
  • This study elucidates a specific signaling cascade relevant to neuroblastoma cell function.

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