Hippo signaling pathway and organ size control - PubMed (original) (raw)

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Hippo signaling pathway and organ size control

Lei Zhang et al. Fly (Austin). 2009 Jan-Mar.

Abstract

Initially discovered in Drosophila, the Hippo (Hpo) pathway has been recognized as a conserved signaling pathway that controls organ size during development by restricting cell growth and proliferation and by promoting apoptosis. In addition, abnormal activities of several Hpo pathway components have been implicated in human cancer. Here, we review the current understanding of the molecular and cellular basis of Hpo signaling in development and tumorigenesis, and discuss how the Hpo pathway integrates spatial and temporal signals to control tissue growth and organ size.

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Figures

Figure 1

Figure 1. hop or wts mutant clones lead to tumor-like growth in mosaic flies

Wild type eye (A) or enlarged eye carrying hpo mutant clones (B_). wts_ mutant clones (arrows) located on the notum resulted in tumor-like growth (C). Adapted from Jia et al.

Figure 2

Figure 2. The Drosophila Hpo pathway

The Hpo kinase cascade consists of four core proteins: Hpo, Sav, Wts, and Mats. Sav binds and regulates Hpo. Hpo phosphorylates and activates Wts. Hpo also phosphorylates Mats to enhance its ability to activate Wts. Wts phosphorylates Yki and restricts its nuclear localization. Yki forms a complex with Sd to activate Hpo target genes. Ex and Mer act in a partially redundant manner to regulate the Hpo kinase cascade. Fat is a candidate receptor and may regulate the Hpo pathway through Dachs and Ex. Ds is a candidate ligand for Fat. Fj modulates Ds/Fat interaction through phosphorylating Ds and Fat in the Golgi.

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