Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Regulation of ERK1/2 by the C. elegans Muscarinic Acetylcholine Receptor GAR-3 in Chinese Hamster Ovary Cells

  • Kim, Seungwoo (School of Life Sciences, Chungbuk National University) ;
  • Shin, Youngmi (School of Life Sciences, Chungbuk National University) ;
  • Shin, Youngju (School of Life Sciences, Chungbuk National University) ;
  • Park, Yang-Seo (School of Life Sciences, Chungbuk National University) ;
  • Cho, Nam Jeong (School of Life Sciences, Chungbuk National University)
  • Received : 2007.10.04
  • Accepted : 2008.02.05
  • Published : 2008.06.30
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Abstract

Three G-protein-linked acetylcholine receptors (GARs) exist in the nematode C. elegans. GAR-3 is pharmacologically most similar to mammalian muscarinic acetylcholine receptors (mAChRs). We observed that carbachol stimulated ERK1/2 activation in Chinese hamster ovary (CHO) cells stably expressing GAR-3b, the predominant alternatively spliced isoform of GAR-3. This effect was substantially reduced by the phospholipase C (PLC) inhibitor U73122 and the protein kinase C (PKC) inhibitor GF109203X, implying that PLC and PKC are involved in this process. On the other hand, GAR-3b-mediated ERK1/2 activation was inhibited by treatment with forskolin, an adenylate cyclase (AC) activator. This inhibitory effect was blocked by H89, an inhibitor of cAMP-dependent protein kinase A (PKA). These results suggest that GAR-3b-mediated ERK1/2 activation is negatively regulated by cAMP through PKA. Together our data show that GAR-3b mediates ERK1/2 activation in CHO cells and that GAR-3b can couple to both stimulatory and inhibitory pathways to modulate ERK1/2.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

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