Figure 8.

CK1 in Hippo signaling in vertebrates. (A) In absence of growth suppressive signals YAP/TAZ promotes tissue growth and differentiation by regulating the activity of different transcription factors in the nucleus, including SMADs and TEADs. (B) Cell-density activated pathway regulation is controlled by multiple upstream branches by activating the core kinase cassette that represses YAP/TAZ driven gene transcription, either by degradation of TAP/TAZ or by forming physical complexes, preventing its nuclear access. Initially, MST1/2 is activated by various components and phosphorylates LATS1/2 (1), which in turn phosphorylates TAP/TAZ on Ser-311 or Ser-381 (2a). This phosphorylation primes YAP/TAZ for further phosphorylation by CK1δ/ε (3a) and consequent recruitment of and ubiquitination by β-TrCP (4a), priming YAP/TAZ for degradation (5a). However, LATS1/2 driven phosphorylation of TAP/TAZ on Ser-127 (2b) leads to the formation of 14-3-3-YAP/TAZ complexes, which accumulate in the cytoplasm preventing YAP/TAZ access to the nucleus (3b). Hippo pathway regulates Wnt/β-catenin signaling by inhibition of DVL, either by MST1/2-mediated prevention of CK1ε-dependent phosphorylation of DVL, or by direct inhibition of DVL by YAP/TAZ. ABCP: apicobasal cell polarity protein.