Fig. 3

Phosphorylation of SNAIL and Par6. (Blue arrowhead indicates sequential patterns. indicates inhibition. Purple arrowhead indicates translocation.) a. SNAIL phosphorylation that suppresses EMT. GSK-3β phosphorylates SNAIL at two consecutive motifs. First, the phosphorylation at the second motif induces the cytoplasmic translocation of SNAIL from the nucleus. In the cytoplasm, SNAIL is phosphorylated on motif 1, and this phosphorylation is recognized by β-Trcp which targets it for proteosomal degradation of SNAIL. PKD1 is another kinase that phosphorylates SNAIL so it can be recognized by β-Trcp and FOXO11 that target it for proteosomal degradation. b. Mechanisms of EMT activation mediated by TGFβR. The activation of TGFβR results in the phosphorylation of Par6, and in turn activation of SMURF1 that targets RHOA degradation by the proteasome, which contributes to the disassembly of the tight junctions