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. 2020 Dec 11;477(23):4603–4621. doi: 10.1042/BCJ20200506

Figure 4. CK1 in Hippo signalling.

Figure 4.

Under conditions of low cell density, the YAP/TAZ transcriptional co-activator complex cycles between the cytosol and nucleus, and in the nucleus YAP/TAZ bind to their cognate transcription factor targets, such as SMADs to trigger transcription of Hippo target genes to promote cell growth and differentiation. CK1 phosphorylates Dvl to promote Wnt signalling under these conditions. Under conditions of cell stress, such as contact inhibition, the kinase MST1/2 becomes activated and phosphorylates LATS1/2, which promotes LATS1/2-mediated phosphorylation of YAP/TAZ. YAP/TAZ phosphorylation acts as a phosphodegron signal to promote YAP/TAZ ubiquitination by β-TrCP, and subsequent YAP/TAZ proteolysis. As YAP/TAZ cannot enter the nucleus, Hippo target gene transcription is suppressed, and cells cease to grow. CK1 has been reported to phosphorylate YAP/TAZ after priming phosphorylation from LATS1/2, and following CK1 binding to MST1/2, CK1 phosphorylation of Dvl is reduced, leading to inhibition of Wnt signalling.