scholarly journals The use of Drosophila Melanogaster as a Model Organism to study the effect of Innate Immunity on Metabolism

2020 ◽  
Author(s):  
Abeer Mohbeddin ◽  
Nawar Haj Ahmed ◽  
Layla Kamareddine
Keyword(s):  
Drosophila Melanogaster ◽  
Fat Body ◽  
Model Organism ◽  
Fruit Fly ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Metabolic Homeostasis ◽  
Stat Signaling ◽  
Stat Pathway

Apart from its traditional role in disease control, recent body of evidence has implicated a role of the immune system in regulating metabolic homeostasis. Owing to the importance of this “immune-metabolic alignment” in dictating a state of health or disease, a proper mechanistic understanding of this alignment is crucial in opening up for promising therapeutic approaches against a broad range of chronic, metabolic, and inflammatory disorders like obesity, diabetes, and inflammatory bowel syndrome. In this project, we addressed the role of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) innate immune pathway in regulating different metabolic parameters using the Drosophila melanogaster (DM) fruit fly model organism. Mutant JAK/STAT pathway flies with a systemic knockdown of either Domeless (Dome) [domeG0282], the receptor that activates JAK/STAT signaling, or the signal-transducer and activator of transcription protein at 92E (Stat92E) [stat92EEY10528], were used. The results of the study revealed that blocking JAK/STAT signaling alters the metabolic profile of mutant flies. Both domeG0282 and stat92EEY10528 mutants had an increase in body weight, lipid deprivation from their fat body (lipid storage organ in flies), irregular accumulation of lipid droplets in the gut, systemic elevation of glucose and triglyceride levels, and differential down-regulation in the relative gene expression of different peptide hormones (Tachykinin, Allatostatin C, and Diuretic hormone 31) known to regulate metabolic homeostasis in flies. Because the JAK/STAT pathway is evolutionary conserved between invertebrates and vertebrates, our potential findings in the fruit fly serves as a platform for further immune-metabolic translational studies in more complex mammalian systems including humans.

scholarly journals The JAK/STAT signaling pathway: from bench to clinic

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaoyi Hu ◽  
Jing li ◽  
Maorong Fu ◽  
Xia Zhao ◽  
Wei Wang
Keyword(s):  
Signaling Pathway ◽  
Current Knowledge ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Quarter Century ◽  
Cellular Processes ◽  
Stat Signaling ◽  
Cancer And Inflammation ◽  
Stat Pathway

AbstractThe Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

scholarly journals The Role and Therapeutic Targeting of JAK/STAT Signaling in Glioblastoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 437
Author(s):  
Alexander Ou ◽  
Martina Ott ◽  
Dexing Fang ◽  
Amy B. Heimberger
Keyword(s):  
Immune Escape ◽  
Janus Kinase ◽  
Molecular Heterogeneity ◽  
Signal Transducer ◽  
Therapeutic Targeting ◽  
Future Directions ◽  
Stem Cell Maintenance ◽  
Current State ◽  
Stat Signaling

Glioblastoma remains one of the deadliest and treatment-refractory human malignancies in large part due to its diffusely infiltrative nature, molecular heterogeneity, and capacity for immune escape. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes substantively to a wide variety of protumorigenic functions, including proliferation, anti-apoptosis, angiogenesis, stem cell maintenance, and immune suppression. We review the current state of knowledge regarding the biological role of JAK/STAT signaling in glioblastoma, therapeutic strategies, and future directions for the field.

scholarly journals Role of the JAK-STAT Pathway in Bovine Mastitis and Milk Production

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2107
Author(s):  
Muhammad Zahoor Khan ◽  
Adnan Khan ◽  
Jianxin Xiao ◽  
Yulin Ma ◽  
Jiaying Ma ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Milk Production ◽  
Critical Role ◽  
Bovine Mastitis ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Production Traits ◽  
Stat Pathway

The cytokine-activated Janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway is a sequence of communications between proteins in a cell, and it is associated with various processes such as cell division, apoptosis, mammary gland development, lactation, anti-inflammation, and immunity. The pathway is involved in transferring information from receptors on the cell surface to the cell nucleus, resulting in the regulation of genes through transcription. The Janus kinase 2 (JAK2), signal transducer and activator of transcription A and B (STAT5 A & B), STAT1, and cytokine signaling suppressor 3 (SOCS3) are the key members of the JAK-STAT pathway. Interestingly, prolactin (Prl) also uses the JAK-STAT pathway to regulate milk production traits in dairy cattle. The activation of JAK2 and STATs genes has a critical role in milk production and mastitis resistance. The upregulation of SOCS3 in bovine mammary epithelial cells inhibits the activation of JAK2 and STATs genes, which promotes mastitis development and reduces the lactational performance of dairy cattle. In the current review, we highlight the recent development in the knowledge of JAK-STAT, which will enhance our ability to devise therapeutic strategies for bovine mastitis control. Furthermore, the review also explores the role of the JAK-STAT pathway in the regulation of milk production in dairy cattle.

scholarly journals The Role of LNK (SH2B3) in the Regulation of JAK-STAT Signalling in Haematopoiesis

2021 ◽  
Vol 15 (1) ◽  
pp. 24
Author(s):  
Rhiannon Morris ◽  
Liesl Butler ◽  
Andrew Perkins ◽  
Nadia J. Kershaw ◽  
Jeffrey J. Babon
Keyword(s):  
Inflammatory Diseases ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Janus Kinase ◽  
Target Cells ◽  
Signal Transducer ◽  
Pathway Activation ◽  
Specific Receptors ◽  
Stat Pathway

LNK is a member of the SH2B family of adaptor proteins and is a non-redundant regulator of cytokine signalling. Cytokines are secreted intercellular messengers that bind to specific receptors on the surface of target cells to activate the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signalling pathway. Activation of the JAK-STAT pathway leads to proliferative and often inflammatory effects, and so the amplitude and duration of signalling are tightly controlled. LNK binds phosphotyrosine residues to signalling proteins downstream of cytokines and constrains JAK-STAT signalling. Mutations in LNK have been identified in a range of haematological and inflammatory diseases due to increased signalling following the loss of LNK function. Here, we review the regulation of JAK-STAT signalling via the adaptor protein LNK and discuss the role of LNK in haematological diseases.

scholarly journals Essential Role of Signal Transducer and Activator of Transcription (Stat)5a but Not Stat5b for Flt3-Dependent Signaling

2000 ◽  
Vol 192 (5) ◽  
pp. 719-728 ◽  
Author(s):  
Shuli Zhang ◽  
Seiji Fukuda ◽  
Younghee Lee ◽  
Giao Hangoc ◽  
Scott Cooper ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Receptor Tyrosine Kinase ◽  
Kinase Activity ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Flt3 Ligand ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Stat Pathway

The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic stem and progenitor cells. Although some post-receptor signaling events of Flt3 have been characterized, the involvement of the Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway in Flt3 signaling has not been thoroughly evaluated. To this aim, we examined whether Flt3 activates the Jak/Stat pathway in Baf3/Flt3 cells, a line stably expressing human Flt3 receptor. Stat5a, but not Stats 1–4, 5b, or 6, was potently activated by Flt3 ligand (FL) stimulation. Interestingly, FL did not activate any Jaks. Activation of Stat5a required the kinase activity of Flt3. A selective role for Stat5a in the proliferative response of primary hematopoietic progenitor cells to FL was documented, as FL did not act on progenitors from marrows of Stat5a−/− mice, but did stimulate/costimulate proliferation of these cells from Stat5a+/+, Stat5b−/−, and Stat5b+/+ mice. Thus, Stat5a is essential for at least certain effects of FL. Moreover, our data confirm that Stat5a and Stat5b are not redundant, but rather are at least partially distinctive in their function.

scholarly journals Quantitative investigation reveals distinct phases in Drosophila sleep

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Xiaochan Xu ◽  
Wei Yang ◽  
Binghui Tian ◽  
Xiuwen Sui ◽  
Weilai Chi ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
General Pattern ◽  
Model Organism ◽  
Infrared Camera ◽  
Fruit Fly ◽  
Genetic Dissection ◽  
Power Law Distribution ◽  
Quantitative Investigation ◽  
Waking Up ◽  
Set Up

AbstractThe fruit fly, Drosophila melanogaster, has been used as a model organism for the molecular and genetic dissection of sleeping behaviors. However, most previous studies were based on qualitative or semi-quantitative characterizations. Here we quantified sleep in flies. We set up an assay to continuously track the activity of flies using infrared camera, which monitored the movement of tens of flies simultaneously with high spatial and temporal resolution. We obtained accurate statistics regarding the rest and sleep patterns of single flies. Analysis of our data has revealed a general pattern of rest and sleep: the rest statistics obeyed a power law distribution and the sleep statistics obeyed an exponential distribution. Thus, a resting fly would start to move again with a probability that decreased with the time it has rested, whereas a sleeping fly would wake up with a probability independent of how long it had slept. Resting transits to sleeping at time scales of minutes. Our method allows quantitative investigations of resting and sleeping behaviors and our results provide insights for mechanisms of falling into and waking up from sleep.

Atomistic insight into the inhibition mechanisms of suppressors of cytokine signaling on Janus kinase

2019 ◽  
Vol 21 (24) ◽  
pp. 12905-12915 ◽  
Author(s):  
Yaru Wei ◽  
Zhiyang Zhang ◽  
Nai She ◽  
Xin Chen ◽  
Yuan Zhao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Negative Feedback ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Jak Kinase ◽  
Stat Signaling ◽  
Suppressors Of Cytokine Signaling ◽  
Insight Into

Suppressors of cytokine signaling (SOCS) act as negative feedback regulators of the Janus kinase/signal transducer (JAK–STAT) signaling pathway by inhibiting the activity of JAK kinase.

scholarly journals JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration

2020 ◽  
Vol 21 (23) ◽  
pp. 9004
Author(s):  
Alexandra Damerau ◽  
Timo Gaber ◽  
Sarah Ohrndorf ◽  
Paula Hoff
Keyword(s):  
Signaling Pathway ◽  
Bone Development ◽  
Gene Knockout ◽  
Selective Inhibition ◽  
Janus Kinase ◽  
General Mechanism ◽  
Stat Signaling ◽  
Skeletal Phenotype ◽  
Pro Inflammatory Cytokines

The Janus kinase (JAK) signal transducer and activator of transcription (STAT) signaling pathway serves as an important downstream mediator for a variety of cytokines, hormones, and growth factors. Emerging evidence suggests JAK/STAT signaling pathway plays an important role in bone development, metabolism, and healing. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. Here, we summarize the role of JAK/STAT pathway on development, homeostasis, and regeneration based on skeletal phenotype of individual JAK and STAT gene knockout models and selective inhibition of components of the JAK/STAT signaling including influences of JAK inhibition in osteoclasts, osteoblasts, and osteocytes.

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