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 Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies

2012 ◽  
Vol 30 (9) ◽  
pp. 1005-1014 ◽  
Author(s):  
Pasquale Sansone ◽  
Jacqueline Bromberg
Keyword(s):  
Interleukin 6 ◽  
Potential Role ◽  
Tumor Formation ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Metastatic Progression ◽  
And Function ◽  
Principal Pathway ◽  
Stat Pathway

The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers.

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 FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE−/− mice atherosclerosis

2021 ◽  
Author(s):  
Lingbo Xu ◽  
Huiping Zhang ◽  
Yanhua Wang ◽  
Anning Yang ◽  
Xiaoyan Dong ◽  
...  
Keyword(s):  
Critical Role ◽  
Elevated Serum ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Membrane Translocation ◽  
Suppressor Of Cytokine Signaling ◽  
Fatty Acid Binding ◽  
Kinase C ◽  
Inflammatory Vascular Disease

AbstractAtherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)—a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE−/− mice.

scholarly journals Targeted Analysis Reveals an Important Role of JAK-STAT-SOCS Genes for Milk Production Traits in Australian Dairy Cattle

2015 ◽  
Vol 6 ◽  
Author(s):  
Sondur J. Arun ◽  
Peter C. Thomson ◽  
Paul A. Sheehy ◽  
Mehar S. Khatkar ◽  
Herman W. Raadsma ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Milk Production ◽  
Production Traits ◽  
Milk Production Traits ◽  
Targeted Analysis

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.

Hijack and exploitation of host SOCS proteins: An immunosuppressive deception of the viruses

2014 ◽  
Vol 3 (6) ◽  
pp. 314-318
Author(s):  
Mansi Shrivastava ◽  
Sarfaraz Alam ◽  
L. K. Dwivedi
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Feedback Loop ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Signal Transducer ◽  
Host Body ◽  
Body Tissues ◽  
Socs Proteins ◽  
Stat Pathway

The suppressors of cytokine signaling (SOCS) are a cytoplasmic protein family that completes a negative feedback loop to attenuate signal transduction from cytokines through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. They work as a natural precaution to pre-vent excessive immune responses that could cause collateral damage to body tissues. But viruses use SOCS proteins to suppress the proportionate immune response also so that a vulnerable environment can be developed in host body to let them grow freely. In several cases, an increased expression of SOCS proteins has been reported in virus infected individuals, which is believed to be induced by the viruses to inhibit the anti-proliferative and antiviral activity of cytokines (Interferon) of host body. Viruses including HIV hijack the expression of SOCS proteins and manipulate them in a way where they support the onset of antigens in host body by suppressing the cell sig-nalling of immune response. Detailed mechanism of the same and an alter-native way to stop viral infection by restoring the normal SOCS expression is discussed in the present review.

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