Li Guangnan, Iyengar Ravi
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13254-9. doi: 10.1073/pnas.202355799. Epub 2002 Sep 18.
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.
信号通路相互作用，以整合和调节引发复杂细胞反应的信息流。我们研究了Gq和Wnt/β-连环蛋白信号通路之间相互作用的机制及后果。在人结肠癌SW480细胞中，通过转录报告基因和细胞增殖试验确定，Gq信号通路的激活抑制β-连环蛋白信号传导。从内部储存库释放的Ca(2+)导致β-连环蛋白在细胞质中发生核输出并被钙蛋白酶介导降解。Gαq并不抑制SW480细胞中组成型激活的DeltaN-XTCF3-VP16嵌合体的作用。同样，在HEK293细胞中，Gq信号通路抑制由Wnt/卷曲蛋白相互作用或糖原合酶激酶-3β抗性β-连环蛋白诱导的β-连环蛋白-T细胞因子/淋巴细胞增强因子-1转录活性，但不抑制DeltaN-XTCF3-VP16。我们得出结论，Gq信号传导促进β-连环蛋白的核输出和钙蛋白酶介导的降解，因此有助于抑制Wnt/β-连环蛋白信号通路。
