Tao-1 Phosphorylates Hippo/MST Kinases to Regulate the Hippo-Salvador-Warts Tumor Suppressor Pathway

Boggiano, Julian C.; Vanderzalm, Pamela J.; Fehon, Richard G.

doi:10.1016/j.devcel.2011.08.028

Cited by 206 publications

(188 citation statements)

References 42 publications

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“…These include the Scribble (Scrib)-Discs large (Dlg)-Lethal giant larvae (Lgl) complex, atypical protein kinase C (aPKC), Crumbs (Crb) , and Echinoid (Ed) (Chen et al, 2010a;Grzeschik et al, 2010;Ling et al, 2010;Robinson et al, 2010;Yue et al, 2012), indicating a role of cell polarity and cell adhesion in Hippo pathway regulation. Furthermore, two studies identified Tao-1, a STE20 family protein kinase as a positive regulator of the Hippo pathway, possibly by directly phosphorylating and activating the Hpo kinase (Boggiano et al, 2011;Poon et al, 2011). In addition, homodimerization was also found to regulate Hpo kinase activity (Jin et al, 2012).…”

Section: The Drosophila Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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This pathway was first found to inhibit cell proliferation and promote apoptosis, therefore regulating cell number and organ size in both Drosophila and mammals. However, in several organs, disturbance of the pathway leads to specific expansion of the progenitor cell compartment and manipulation of the pathway in embryonic stem cells strongly affects their self-renewal and differentiation. In this review, we summarize current observations on roles of the Hippo pathway in different types of stem cells and discuss how these findings changed our view on the Hippo pathway in organ development and tumorigenesis.

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Section: The Drosophila Hippo Pathwaymentioning

confidence: 99%

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

et al. 2012

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“…Mechanistically, the Hippo kinase cascade can be initiated by TAO kinases (TAOK1/2/3), which phosphorylate the activation loop of MST1/2 (Thr183 for MST1 and Thr180 for MST2; hereafter, all residues refer to human proteins) and thereby lead to MST1/2 activation (Boggiano et al 2011;Poon et al 2011). There is also evidence showing that the activation loop phosphorylation can be achieved by MST1/2 autophosphorylation (Praskova et al 2004).…”

Section: Core Components Of the Mammalian Hippo Pathwaymentioning

confidence: 99%

Mechanisms of Hippo pathway regulation

2016

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The Hippo pathway was initially identified in Drosophila melanogaster screens for tissue growth two decades ago and has been a subject extensively studied in both Drosophila and mammals in the last several years. The core of the Hippo pathway consists of a kinase cascade, transcription coactivators, and DNA-binding partners. Recent studies have expanded the Hippo pathway as a complex signaling network with >30 components. This pathway is regulated by intrinsic cell machineries, such as cell–cell contact, cell polarity, and actin cytoskeleton, as well as a wide range of signals, including cellular energy status, mechanical cues, and hormonal signals that act through G-protein-coupled receptors. The major functions of the Hippo pathway have been defined to restrict tissue growth in adults and modulate cell proliferation, differentiation, and migration in developing organs. Furthermore, dysregulation of the Hippo pathway leads to aberrant cell growth and neoplasia. In this review, we focus on recent developments in our understanding of the molecular actions of the core Hippo kinase cascade and discuss key open questions in the regulation and function of the Hippo pathway.

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“…RNA interference (RNAi) lines obtained from the Bloomington Drosophila Stock Center or Vienna Drosophila Resource Center have been tested in previous studies (Das Thakur et al 2010;Genevet et al 2010;Boggiano et al 2011;Reddy and Irvine 2011;Chen and Verheyen 2012;Nagaraj et al 2012;Poernbacher et al 2012;Jukam et al 2013). slbo-Gal4-driven UAS-GFP flies were used as controls.…”

Section: Overexpression Of Hpo In Outer Border Cells Disrupts Bordermentioning

confidence: 99%

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

Lin¹,

Yeh²,

Wang

et al. 2014

Genetics

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The Hippo pathway is a key signaling cascade in controlling organ size. The core components of this pathway are two kinases, Hippo (Hpo) and Warts (Wts), and a transcriptional coactivator, Yorkie (Yki). Yes-associated protein (YAP, a Yki homolog in mammals) promotes epithelial-mesenchymal transition and cell migration in vitro. Here, we use border cells in the Drosophila ovary as a model to study Hippo pathway functions in cell migration in vivo. During oogenesis, polar cells secrete Unpaired (Upd), which activates JAK/STAT signaling of neighboring cells and specifies them into outer border cells. The outer border cells form a cluster with polar cells and undergo migration. We find that hpo and wts are required for migration of the border cell cluster. In outer border cells, overexpression of hpo disrupts polarization of the actin cytoskeleton and attenuates migration. In polar cells, knockdown of hpo and wts or overexpression of yki impairs border cell induction and disrupts migration. These manipulations in polar cells reduce JAK/STAT activity in outer border cells. Expression of upd-lacZ is increased and decreased in yki and hpo mutant polar cells, respectively. Furthermore, forced expression of upd in polar cells rescues defects of border cell induction and migration caused by wts knockdown. These results suggest that Yki negatively regulates border cell induction by inhibiting JAK/STAT signaling. Together, our data elucidate two distinct mechanisms of the Hippo pathway in controlling border cell migration: (1) in outer border cells, it regulates polarized distribution of the actin cytoskeleton; (2) in polar cells, it regulates upd expression to control border cell induction and migration.

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Tao-1 Phosphorylates Hippo/MST Kinases to Regulate the Hippo-Salvador-Warts Tumor Suppressor Pathway

Cited by 206 publications

References 42 publications

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

The Hippo pathway regulates stem cell proliferation, self-renewal, and differentiation

Mechanisms of Hippo pathway regulation

The Hippo Pathway Controls Border Cell Migration Through Distinct Mechanisms in Outer Border Cells and Polar Cells of the Drosophila Ovary

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