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KMID : 0578320080250040504
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Molecules and Cells
2008 Volume.25 No. 4 p.504 ~ p.509
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Regulation of ERK1/2 by the C. elegans Muscarinic Acetylcholine Receptor GAR-3 in Chinese Hamster Ovary Cells
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Kim Seung-Woo
Cho Nam-Jeong
Shin Young-Mi
Shin Young-Ju
Park Yang-Seo
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Abstract
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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.
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KEYWORD
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C. elegans, ERK1/2, GAR-3, Muscarinic Acetylcholine Receptor
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