title: Calpain as an effector of the Gq signaling pathway for inhibition of Wnt/beta -catenin-regulated cell proliferation.
abstract: Signaling pathways interact to integrate and regulate information flow in evoking complex cellular responses. We have studied the mechanisms and consequences of interactions between the Gq and Wnt/beta-catenin pathways. In human colon carcinoma SW480 cells, activation of the Gq pathway inhibits beta-catenin signaling as determined by transcriptional reporter and cell proliferation assays. Ca(2+) release from internal stores results in nuclear export and calpain-mediated degradation of beta-catenin in the cytoplasm. Galphaq does not inhibit the effects of constitutively activated DeltaN-XTCF3-VP16 chimera in SW480 cells. Similarly, in HEK293 cells the Gq pathway suppresses beta-catenin-T cell factor/lymphocyte enhancer factor-1 transcriptional activity induced by Wnt/Frizzled interaction or glycogen synthase kinase-3beta-resistant beta-catenin, but not DeltaN-XTCF3-VP16. We conclude that Gq signaling promotes nuclear export and calpain-mediated degradation of beta-catenin, which therefore contributes to the inhibition of Wnt/beta-catenin pathway.
authors.affiliation: Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Guangnan
authors.initials: G
authors.lastname: Li
authors.forename: Ravi
authors.initials: R
authors.lastname: Iyengar
mesh_terms: D002118:Calcium / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism* / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D002154:Calpain; D019204:GTP-Binding Proteins; D002118:Calcium