Processing and phosphorylation of the Fat receptor

Feng, Yang; Irvine, Kenneth D.

doi:10.1073/pnas.0811540106

Cited by 94 publications

(152 citation statements)

References 23 publications

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“…Our data gathered from the dco, wts and hpo mutant clones therefore were consistent with our results obtained from RNAi-depleted tissues, with both approaches revealing strong caffeine-dependent phenotypes. As Dco is known to promote Wts activity downstream of Ft, 44 we tested the effect of ft knock down in the developing eye of animals in the presence or absence of caffeine. This resulted in a slightly rough eye phenotype in caffeine-treated animals (data not shown).…”

Section: Resultsmentioning

confidence: 99%

The Hippo pathway promotes cell survival in response to chemical stress

Cara

Maile²,

Parsons

et al. 2015

Cell Death Differ

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Cellular stress defense mechanisms have evolved to maintain homeostasis in response to a broad variety of environmental challenges. Stress signaling pathways activate multiple cellular programs that range from the activation of survival pathways to the initiation of cell death when cells are damaged beyond repair. To identify novel players acting in stress response pathways, we conducted a cell culture RNA interference (RNAi) screen using caffeine as a xenobiotic stress-inducing agent, as this compound is a well-established inducer of detoxification response pathways. Specifically, we examined how caffeine affects cell survival when Drosophila kinases and phosphatases were depleted via RNAi. Using this approach, we identified and validated 10 kinases and 4 phosphatases that are essential for cell survival under caffeine-induced stress both in cell culture and living flies. Remarkably, our screen yielded an enrichment of Hippo pathway components, indicating that this pathway regulates cellular stress responses. Indeed, we show that the Hippo pathway acts as a potent repressor of stress-induced cell death. Further, we demonstrate that Hippo activation is necessary to inhibit a pro-apoptotic program triggered by the interaction of the transcriptional co-activator Yki with the transcription factor p53 in response to a range of stress stimuli. Our in vitro and in vivo loss-of-function data therefore implicate Hippo signaling in the transduction of cellular survival signals in response to chemical stress. Throughout their lives, organisms are exposed to a wide range of harmful substances. These compounds, often referred to as xenobiotics, may enter the body through direct contact, inhalation or ingestion, and can originate from many sources including pharmaceuticals, pesticides, plant toxins and pollutants. The ubiquitous and varied nature of xenobiotic pressure is reflected in the complexity of conserved cellular defense mechanisms that respond to these chemical compounds, and metazoans have thus developed a range of pathways that activate survival responses or trigger programmed cell death to eliminate damaged cells. 1 Xenobiotic pathways control the expression and activation of heat shock proteins, oxidative stress components, DNA repair enzymes, hypoxia response factors and several groups of xenobiotic-metabolizing enzymes. In eukaryotes, environmental challenges that activate stress response programs are relayed through a complex signaling cascade. Some stress pathways respond to very specific compounds, whereas others, such as those depending on Mitogen-activated protein kinases, propagate stress signals from a broad spectrum of stimuli. 1-3 Despite the importance that stress response pathways play in pharmacology and toxicology, we still have a relatively poor understanding of the complex networks that launch these cellular defense systems.We performed a quantitative cell-culture RNA interference (RNAi) assay of Drosophila kinases and phosphatases to identify key regulators of stress response pathways that reac...

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Section: Resultsmentioning

confidence: 99%

The Hippo pathway promotes cell survival in response to chemical stress

Cara

Maile²,

Parsons

et al. 2015

Cell Death Differ

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“…Removing one copy of yki dramatically suppressed the fat mutant overgrowth phenotype (Bennett and Harvey, 2006;Silva et al, 2006;Willecke et al, 2006), indicating that yki is an important mediator of fat function. Fat activity is regulated by binding to another protocadherin, Dachsous (Ds) (Matakatsu and Blair, 2006), and is modulated by several proteins such as the casein kinase Discs overgrown (Dco) (Feng and Irvine, 2009;Sopko et al, 2009), the Golgi-resident kinase Four-jointed (Fj) (Rogulja et al, 2008;Willecke et al, 2008;Simon et al, 2010), and the Fat/Ds-interacting protein Lowfat (Lft) (Mao et al, 2009). A LIM domain-containing protein Zyxin (Zyx) also inhibits Hippo signaling possibly by physical interaction with Wts and Dachs downstream of Fat (Rauskolb et al, 2011).…”

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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“…Transcription of fat, dachsous, four-jointed, expanded and merlin are enhanced by loss of Hippo pathway activity, providing negative feedback, and also allowing changes in Hippo activity to be transmitted to adjacent cells. Fat also binds Casein Kinase Iε, which promotes Hpo pathway activity 69,70 . There are multiple interactions between the upstream components.…”

Section: Growth Control By Fat Pcp Regulatorsmentioning

confidence: 99%

When pathways collide: collaboration and connivance among signalling proteins in development

McNeill

Woodgett

2010

Nat Rev Mol Cell Biol

143

106

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Signal transduction pathways interact at various levels in defining tissue morphology, size and differentiation during development. Understanding of the mechanisms by which these pathways collude has been greatly enhanced by recent insights into how shared components are independently regulated and how the activity of one system is contextualized by others. Traditionally, the components of signalling pathways have been assumed to show pathway fidelity and to act with a high degree of autonomy. However, as illustrated by the Wnt and Hippo pathways, there is increasing evidence that components are often shared between multiple pathways and other components talk to each other through multiple mechanisms.

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Processing and phosphorylation of the Fat receptor

Cited by 94 publications

References 23 publications

The Hippo pathway promotes cell survival in response to chemical stress

The Hippo pathway promotes cell survival in response to chemical stress

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

When pathways collide: collaboration and connivance among signalling proteins in development

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