Par-1 Regulates Tissue Growth by Influencing Hippo Phosphorylation Status and Hippo-Salvador Association
Figure 7
MARK, the mammalian homologue of Par-1, regulates the Hpo pathway.
(A) MARK4 activates YAP transcriptional activity. The indicated plasmids were co-transfected with the 5XUAS-luc reporter, Gal4-TEAD4, Flag-YAP, and CMV-β-galactosidase construct into HEK293T cells. Luciferase activity was measured and normalized against β-galactosidase activity. (B) Ectopic expression of MARK4 inhibits YAP phosphorylation. HEK293T cells were transfected with the indicated constructs, and YAP was immunoprecipitated using the anti-Flag antibody. YAP phosphorylation was detected using Western blot analysis with a phospho-YAP specific antibody and determining its mobility on a Phos-tag-containing SDS-PAGE gel. (C) MARK4 induces the phosphorylation of MST2. HEK293T cells were transfected with the indicated constructs, and MST2 phosphorylation was analyzed by electrophoresis on a Phos-tag-containing gel and through Western blotting with an anti-Flag antibody. (D) MARK1 expression is significantly upregulated in squamous lung cancer biopsy specimens compared with matched control specimens. The expression profiling data were downloaded from the GEO dataset GDS1312. These data were expressed as the mean ± SEM and were analyzed using the paired t-test. *p<0.05. (E) Prostate cancer progression is accompanied by an increased expression of MARK1. PIN, prostatic intraepithelial neoplasia; PCA, localized prostate cancer; MET, metastatic prostate cancer. The expression data were obtained from GEO dataset GDS3289. All of the results were expressed as the mean ± SEM. ***p<0.001.