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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)
Publication Information
Molecules and Cells / v.25, no.4, 2008 , pp. 504-509 More about this Journal
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
C. elegans; ERK1/2; GAR-3; Muscarinic Acetylcholine Receptor;
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