JAK/STAT signaling in stem cells and regeneration: from<i>Drosophila</i>to vertebrates

Herrera, Salvador C.; Bach, Erika A.

doi:10.1242/dev.167643

Cited by 145 publications

(117 citation statements)

References 190 publications

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“…The interleukin (IL)6 type ligands Upd1 (that is, os), Upd2, and Upd3 bind to their receptor Domeless, which stimulates its dimerization and activation of the associated Janus Kinase (Jak) molecule Hopscotch (Hop). Hop, in turn, phosphorylates the sole Stat ortholog in Drosophila, Stat92E [20]. Activation of Stat92E promotes the growth, proliferation, invasion, and survival of tumor cells [41,42,45,101].…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Hamaratoǧlu

Atkins

2020

IJMS

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Can hyperactivation of a few key signaling effectors be the underlying reason for the majority of epithelial cancers despite different driver mutations? Here, to address this question, we use the Drosophila model, which allows analysis of gene expression from tumors with known initiating mutations. Furthermore, its simplified signaling pathways have numerous well characterized targets we can use as pathway readouts. In Drosophila tumor models, changes in the activities of three pathways, Jun N-terminal Kinase (JNK), Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT), and Hippo, mediated by AP-1 factors, Stat92E, and Yorkie, are reported frequently. We hypothesized this may indicate that these three pathways are commonly deregulated in tumors. To assess this, we mined the available transcriptomic data and evaluated the activity levels of eight pathways in various tumor models. Indeed, at least two out of our three suspects contribute to tumor development in all Drosophila cancer models assessed, despite different initiating mutations or tissues of origin. Surprisingly, we found that Notch signaling is also globally activated in all models examined. We propose that these four pathways, JNK, JAK/STAT, Hippo, and Notch, are paid special attention and assayed for systematically in existing and newly developed models.

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Section: Jak/stat Pathwaymentioning

confidence: 99%

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Hamaratoǧlu

Atkins

2020

IJMS

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“…This pathway is an important means of responding to WNV in both insects (10,44) and mammals (52,53). Because JAK/STAT is related to other regulatory processes like cell proliferation and differentiation [reviewed in (54)], researchers have also used the Drosophila model to study the pathway's role in a non-immunological context like cellular growth (47), differentiation (48), polarization (49), and oogenesis (55). Drosophila provide a unique system for studying JAK/STAT signaling at various levels of complexity in both an immune and regulatory context to provide clarity regarding the pathway's significance in the organism.…”

Section: Jak/stat Pathwaymentioning

confidence: 99%

Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster

Trammell

Goodman

2019

Front. Immunol.

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Arboviruses (arthropod-borne viruses), such as Zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, include some of the most significant global health risks to human populations. The steady increase in the number of cases is of great concern due to the debilitating diseases associated with each viral infection. Because these viruses all depend on the mosquito as a vector for disease transmission, current research has focused on identifying immune mechanisms used by insects to effectively harbor these viruses and cause disease in humans and other animals. Drosophila melanogaster are a vital model to study arboviral infections and host responses as they are a genetically malleable model organism for experimentation that can complement analysis in the virus' natural vectors. D. melanogaster encode a number of distinct mechanisms of antiviral defense that are found in both mosquito and vertebrate animal systems, providing a viable model for study. These pathways include canonical antiviral modules such as RNA interference (RNAi), JAK/STAT signaling, and the induction of STING-mediated immune responses like autophagy. Insulin signaling plays a significant role in host-pathogen interactions. The exact mechanisms of insulin-mediated immune responses vary with each virus type, but nevertheless ultimately demonstrates that metabolic and immune signaling are coupled for antiviral immunity in an arthropod model. This mini review provides our current understanding of antiviral mechanisms in D. melanogaster, with a focus on insulin-mediated antiviral signaling, and how such immune responses pertain to disease models in vertebrate and mosquito species.

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“…The JAK/STAT signaling pathway is required for the differentiation and maturation of ECs, and knockdown of STAT92E, the transcription factor at the end of the JAK/STAT signaling pathway, results in the formation of EB containing tumors (Zhai et al, 2015). Under normal conditions, STAT92E induces the progenitors to differentiate into ECs via regulating Notch activity (Herrera and Bach, 2019). Under stress conditions, like bacterial infection, secreted Unpaired3 (Upd3), a cytokine signal of the JAK/STAT pathway, activates ISC proliferation and differentiation to repair damaged parts of the gut (Buchon et al, 2009;Lin et al, 2010).…”

Section: Transcription Factor Stat92e Of the Jak/stat Pathway Regulatmentioning

confidence: 99%

“…JAK/STAT signaling is known to stimulate progenitor cell differentiation to regulate normal tissue homeostasis (Herrera and Bach, 2019). Under these normal conditions, it also downregulates a-PheRS levels and, consequently, activates Notch signaling at least partially through downregulating a-PheRS levels to promote differentiation of the progenitor cells into ECs.…”

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confidence: 99%

α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain

Suter

2019

Preprint

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Phenylalanyl tRNA synthetase (PheRS) levels are elevated in multiple cancers and, interestingly, also in normal stem cells. Our results show that elevated levels of the α-PheRS subunit stimulate cell proliferation in different tissues, while its downregulation reduces organ size. Importantly, the proliferative activity of α-PheRS is independent of its aminoacyl tRNA synthase (aaRS) activity and does not visibly stimulate translation. Furthermore, stem cell-

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JAK/STAT signaling in stem cells and regeneration: fromDrosophilato vertebrates

Cited by 145 publications

References 190 publications

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Rounding up the Usual Suspects: Assessing Yorkie, AP-1, and Stat Coactivation in Tumorigenesis

Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster

α-Phenylalanyl tRNA synthetase competes with Notch signaling through its N-terminal domain

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