JAK: Not Just Another Kinase

Agashe, Ruchi; Lippman, Scott M.; Kurzrock, Razelle

doi:10.1158/1535-7163.mct-22-0323

Cited by 43 publications

(22 citation statements)

References 67 publications

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“…It is predominantly expressed in marrow cells, thymocytes, NK cells, activated B cells, and activated T cells. It also transduces a signal in response to its activation via tyrosine phosphorylation by interleukin receptors 25 . STAT3 was the substrate and downstream signal molecule of JAK kinase, responsible for regulating gene transcription and signal transduction 26 .…”

Section: Discussionmentioning

confidence: 99%

Immunological and Prognostic Role of Hub Genes Defined Gene Signature in Septic Cardiomyopathy

Yang

Cao

et al. 2023

Preprint

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Septic cardiomyopathy is a life-threatening heart dysfunction caused by severe infection. Considering the complexity of the pathogenesis and high mortality, it was necessary to identify efficient biomarkers to guide the clinical practice. Based on the muti-microarray analysis, this study aimed to explore the pathogenesis of septic cardiomyopathy and the related immune landscape. The results showed that septic cardiomyopathy was organ dysfunction after extreme pro- and anti-inflammation. In this process, KLRG1, PRF1, BCL6, GAB2, MMP9, IL1R1, JAK3, IL6ST, and SERPINE1 were identified as the hub genes regulated the immune landscape of septic cardiomyopathy. Nine transcription factors regulated their expression: SRF, STAT1, SP1, RELA, PPARG, NFKB1, PPARA, SMAD3, and STAT3. Hub genes activated the Th17 cell differentiation pathway, JAK-STAT signaling pathway, and Cytokine-cytokine receptor interaction pathway. These were mainly involved in regulating inflammatory response, adaptive immune response, leukocyte-mediated immunity, cytokine-mediated immunity, immune effector process, myeloid cell differentiation, and T-helper cell differentiation. These nine hub genes can be seen as biomarkers for the early prediction of septic cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

Immunological and Prognostic Role of Hub Genes Defined Gene Signature in Septic Cardiomyopathy

Yang

Cao

et al. 2023

Preprint

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“…[29,30] There are 4 JAKs proteins, which can be divided into JAK1, JAK2, JAK3, and TYK2, while there are 7 STATs proteins, which can be divided into STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6. [31] When cells are stimulated exogenously, JAKs proteins bind to cytokine receptors in a non-covalent manner and mediate receptor tyrosine phosphorylation, which then binds to growth factor STATs to form complexes and is transported into the nucleus as a transcription factor to play a biological role. [32] Studies have shown that the main molecules involved in the pathogenesis of osteosarcoma are JAK2, TYK2, STAT1, STAT2, STAT3, and STAT5A.…”

Section: Jak/stat3 Signaling Pathwaymentioning

confidence: 99%

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Liu,

Jiang,

et al. 2024

Medicine

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Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of “multiple targets and multiple pathways,” and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/β-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-β (TGF-β)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

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“…However, once IFN-I binds to IFNAR, they are automatically activated by transphosphorylation. Subsequently, JAKs promote the phosphorylation of the intracellular tails of specific tyrosine receptors, which provides a docking point for members of the STAT family of transcription factors [96]. To ensure that the signal can be properly switched off, it has been reported that suppressors of cytokine signaling (SOCS) proteins are negative feedback inhibitors of the signal cascade, which inhibit JAKs activity or target IFN-I-induced signaling components for ubiquitination and subsequent proteolysis [97][98][99].…”

Section: Jak1 and Tyk2mentioning

confidence: 99%

Ubiquitination network in the type I IFN‐induced antiviral signaling pathway

et al. 2023

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Type I IFN (IFN‐I) is the body's first line of defense against pathogen infection. IFN‐I can induce cellular antiviral responses and therefore plays a key role in driving antiviral innate and adaptive immunity. Canonical IFN‐I signaling activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, which induces the expression of IFN‐stimulated genes and eventually establishes a complex antiviral state in the cells. Ubiquitin is a ubiquitous cellular molecule for protein modifications, and the ubiquitination modifications of protein have been recognized as one of the key modifications that regulate protein levels and/or signaling activation. Despite great advances in understanding the ubiquitination regulation of many signaling pathways, the mechanisms by which protein ubiquitination regulates IFN‐I‐induced antiviral signaling have not been explored until very recently. This review details the current understanding of the regulatory network of ubiquitination that critically controls the IFN‐I‐induced antiviral signaling pathway from three main levels, including IFN‐I receptors, IFN‐I‐induced cascade signals, and effector IFN‐stimulated genes.

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JAK: Not Just Another Kinase

Cited by 43 publications

References 67 publications

Immunological and Prognostic Role of Hub Genes Defined Gene Signature in Septic Cardiomyopathy

Immunological and Prognostic Role of Hub Genes Defined Gene Signature in Septic Cardiomyopathy

Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets

Ubiquitination network in the type I IFN‐induced antiviral signaling pathway

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