Introduction to the hippo signaling pathway

• Hippo signaling pathway is a signaling cascade that is critical for organ size control.
• It was first identified in Drosophila and named for one of several important kinases involved.
• Unlike other signaling pathways, Hippo does not have a dedicated ligand or receptor.

Discovery of Hippo Pathway

• The loss of Hippo in Drosophila results in excessive growth, leading to a “hippopotamus” phenotype.
• This loss of Hippo leads to an increase in cell division and a decrease in apoptosis.

Key Players in the Hippo Pathway

• The pathway begins with cell-to-cell interactions involving cell adhesion molecules like E-cadherin or Crumbs.
• Angiomotin, an F-actin binding protein, is involved in activating the Hippo kinase cascade.
• The main kinase in the cascade is Large tumor suppressor 1/2 (Lats1/2), which functions to phosphorylate Yorkie or its mammalian homologue Yap/Taz.

Function of Yap/Taz

• Phosphorylation of Yap/Taz results in its retention in the cytoplasm or degradation.
• Lack of Hippo signaling frees Yap/Taz to enter the nucleus and function as a transcription co-activator of Tead.

Interaction with Other Pathways

• The Hippo pathway can regulate the pathways of other paracrine factors like Wnts, EGF, TGF-β, and BMP.
• These pathways can also modulate Hippo signaling, typically through Yap/Taz.

Conclusion

• The Hippo pathway is emerging as a major crossroad for the biochemical pathways of the cell, highlighting the need for understanding how all these pathways are integrated.