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Kibra Functions as a Tumor Suppressor Protein that Regulates Hippo Signaling in Conjunction with Merlin and Expanded
Open accessAbstract
Summary The Hippo signaling pathway regulates organ size and tissue homeostasis from Drosophila to mammals. Central to this pathway is a kinase cascade wherein Hippo (Hpo), in complex with Salvador (Sav), phosphorylates and activates Warts (Wts), which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein, known as the YAP coactivator in mammalian cells. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are upstream components that regulate Hpo activity through unknown mechanisms. Here we identify Kibra (Kbr) as another upstream component of the Hippo signaling pathway. We show that Kbr functions together with Mer and Ex in a protein complex localized to the apical domain of epithelial cells, and that this protein complex regulates the Hippo kinase cascade via direct binding to Hpo and Sav. These results shed light on the mechanism of Ex and Mer function, and implicate Kbr as a potential tumor suppressor with relevance to neurofibromatosis.
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Metadata
- Authors
- Yu, J., Zheng, Y., Dong, J., Klusza, S., Deng, W.-M., & Pan, D.
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 18
- Issue
- 2
- Pages
- 288-299
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2091427349
- Cited by
- 496
- References
- 7
- FWCI
- 18.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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