Figure 1. Schematic representation of the Hippo pathway. (A) Input from divergent upstream pathways activates the core Hippo pathway. Activated Lats kinase phosphorylates Yap, leading to its cytoplasmic retention and degradation. Without nuclear Yap, the expression of Tead target genes is suppressed. In contrast, when Hippo signaling is inactive, Yap enters the nucleus, complexes with Tead, and activates the transcription of target genes. (B) The domain structures of Amot family proteins and Amot-interacting proteins. The numbers at the right of each scheme indicate the numbers of amino acid residues of the proteins. Amot has two isoforms: p130 (Amot130) and p80 (Amot80). Amot80 lacks an N-terminal domain. The N-terminal domain of Amot 130 contains three PY motifs. Yap interacts with the first two PY motifs,23-25,50 and Kibra interacts with the third PY motif.9 The third PY motif is not present in Amotl2. The Amot N-terminal domain also interacts with F-actin. A Lats phosphorylation site (asterisk, S176) is present within the essential region of the Amot F-actin binding domain.34 Merlin interacts with the coiled-coil domain of Amot.21 The interaction of Amot with Lats requires both the N-terminal and coiled-coil domains, but the exact interaction motifs remain unknown.9,22