Fig. 4. Warts signaling pathways. A cellular perspective of Warts signaling pathways. (A) In the Warts `on' (phosphorylated) state, Dachs is inhibited by Fat and not detected at the plasma membrane, and does not decrease Warts levels. Discs overgrown (Dco) promotes Fat signaling upstream of Dachs, through an undetermined mechanism. Expanded accumulates at the membrane, and Expanded and Merlin are activated by unknown regulators, and, in mammalian cells, by CD44. Expanded and Merlin promote Hpo phosphorylation (P), which in turn promotes phosphorylation of Salvador (Sav), Warts and Mob-as-tumor suppressor (Mats), contributing to the assembly of these proteins into complexes. Active Warts phosphorylates Yorkie (Yki), which inhibits Yki by promoting its association with 14-3-3 proteins in the cytoplasm, thereby excluding it from the nucleus. (B) In the Warts `off' (unphosphorylated) state, Dachs accumulates at the membrane, reduces levels of Warts protein and reduces levels of Ex protein at the membrane. Merlin is in its inactive, phosphorylated, state. Components of the Hippo (Hpo) kinase cassette are unphosphorylated, and interactions between them are reduced. Yki is not phosphorylated, and enters the nucleus where it complexes with Scalloped (Sd) to promote the transcription of downstream target genes.