title: Muscarinic acetylcholine receptors mediate eIF4B phosphorylation in SNU-407 colon cancer cells.
abstract: 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.
authors: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, South Korea.
authors: Ziyu
authors: Z
authors: Liu
authors: Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju 28644, South Korea. Electronic address: namjcho@cbnu.ac.kr.
authors: Nam Jeong
authors: NJ
authors: Cho
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*
chemical_list: D039642:Eukaryotic Initiation Factors; D011976:Receptors, Muscarinic; C031799:eIF-4B; D011493:Protein Kinase C
keywords: ERK1/2; Muscarinic acetylcholine receptor; Protein kinase C; SNU-407 colon cancer cell; eIF4B