Lats2 inhibits Wnt signaling.

Abstract

<p>(A) The protein levels of p-DVL2, β-catenin and Wnt signaling targets decrease during adipocyte differentiation. Total cell lysates were prepared from differentiating 3T3L1 cells. (B) Lats2-mediated decrease in β-catenin level. Western blot shows that the levels of DVL2 phosphorylation and β-catenin protein are both reduced by Lats2. (C) Lats2 suppresses the Wnt3a-induced activity of the TOPflash reporter. TOPflash and pRL-TK plasmids were co-transfected into Lats2-transfected cells and the two control (Vector and Control) cells, which were then treated with or without Wnt3a (50 ng/ml). The pRL-TK plasmid (<i>pRenilla</i>) was used as an internal control. The FOPflash assay was used as a negative control. NM, normal medium. (D) and (E) Lats2 inhibits Wnt target gene expression. Quantitative RT-PCR results from Lats2-transfected cells indicate that Pref-1, LEF1, cyclin D1, and c-Myc mRNA levels are reduced by Lats2. The data shown are the means+S.D. of three independent experiments. Western blot shows that the protein levels of cyclin D1, c-Myc, LEF1 and Axin are also reduced by Lats2. In (C) and (D), <i>P</i>-values were calculated using the Student’s t-test (*, <i>P</i><0.05; **, <i>P</i><0.01).</p