期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：20
页码：13254-13259
DOI：10.1073/pnas.202355799
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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. Ca2+ release from internal stores results in nuclear export and calpain-mediated degradation of {beta}-catenin in the cytoplasm. Gq does not inhibit the effects of constitutively activated {Delta}N-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-3{beta}-resistant {beta}-catenin, but not {Delta}N-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.
