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      Muscarinic acetylcholine receptors mediate eIF4B phosphorylation in SNU-407 colon cancer cells

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      https://www.riss.kr/link?id=A107440130

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      다국어 초록 (Multilingual Abstract)

      <P><B>Abstract</B></P> <P>We have previously shown that muscarinic acetylcholine receptors (mAChRs) promote global protein biosynthesis in SNU-407 colon cancer cells. To gain insight into the molecular mechanisms underly...

      <P><B>Abstract</B></P> <P>We have previously shown that muscarinic acetylcholine receptors (mAChRs) promote global protein biosynthesis in SNU-407 colon cancer cells. To gain insight into the molecular mechanisms underlying this event, we examined whether mAChRs regulate the phosphorylation of eIF4B (eukaryotic initiation factor 4B), an essential component of the translation machinery. When SNU-407 cells were treated with the cholinergic agonist carbachol, eIF4B was phosphorylated in a dose- and time-dependent manner. This carbachol effect was almost completely blocked by the muscarinic antagonist atropine, demonstrating that mAChRs specifically mediate the phosphorylation of eIF4B. Carbachol-stimulated eIF4B phosphorylation was significantly reduced by the MEK1/2 inhibitor U0126, indicating that the MEK1/2-ERK1/2 pathway plays an important role in mAChR-mediated eIF4B phosphorylation. However, treating the cells with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 or the mTORC1 (mammalian target of rapamycin complex 1) inhibitor rapamycin had little effect on carbachol-stimulated eIF4B phosphorylation, suggesting that PI3K and mTORC1 are not the key participants in this process. We also observed that the inhibition of protein kinase C (PKC) by GF109203X greatly diminished carbachol-stimulated eIF4B phosphorylation. Together, our data show that mAChRs modulate eIF4B phosphorylation via the ERK1/2 and PKC signaling pathways in SNU-407 colon cancer cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Muscarinic acetylcholine receptors (mAChRs) mediate eIF4B phosphorylation. </LI> <LI> The ERK1/2 signaling pathway is required for mAChR-mediated eIF4B phosphorylation. </LI> <LI> The PI3K-mTORC1 pathway is not important for mAChR-mediated eIF4B phosphorylation. </LI> <LI> Protein kinase C is involved in mAChR-mediated eIF4B phosphorylation. </LI> </UL> </P>

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