STAT5 as a Key Protein of Erythropoietin Signalization

Tóthová, Zuzana; Tomc, Jana; Debeljak, Nataša; Solár, Peter

doi:10.3390/ijms22137109

Cited by 33 publications

(18 citation statements)

References 100 publications

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“…The binding stimulates a member of the tyrosine kinase family, specifically JAK2 to donate a phosphate to the signal transducer and activator of transcription 5 (STAT5). JAK2/STAT5 functioning is therefore essential for erythropoiesis [ 33 ]. CIS3 binds to the EPOR and JAK2 and impairs the normal functioning of this mechanism.…”

Section: Discussionmentioning

confidence: 99%

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19

et al. 2023

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COVID-19 produces cytokine-mediated persistent inflammation and is associated with elevated iron stores and low circulating iron. It is believed that central to the pathophysiological mechanism is interleukin 6 and hepcidin. A state of iron overload, termed hyperferritinemia, and inflammatory anemia take place. Both conditions are linked to a worse result in critically ill patients. Blocking the interleukin 6—hepcidin pathway with Tocilizumab could present favorable outcomes. The aim of this study was to evaluate if Tocilizumab influences survival, the occurrence of sepsis, anemia and transfusions in critically ill patients suffering from COVID-19. This prospective observational study focused on levels of interleukin 6, hepcidin and blood iron parameters in patients treated with Tocilizumab. Data were compared before and after therapy as well as between treated and control groups. Results indicate that there is no difference in terms of survival nor in the rate of anemia or sepsis occurrence. Hepcidin was elevated and anemia ensued after treatment, which could indicate alternative pathways. In conclusion, when the classic interleukin 6—hepcidin pathway is blocked, inflammation seems to use alternative routes. Further understanding of these pathways is required and new pharmacological therapies need to be developed to treat persistent inflammation.

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Section: Discussionmentioning

confidence: 99%

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19

et al. 2023

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“…1) and controls the generation of red blood cells. The EPOR/JAK2/STAT5 pathway is a well established regulator of the differentiation, proliferation, and survival of erythroid progenitor cells [39 ▪ ]. The JAK-STAT pathway significantly influences the formation of the immune system and hematopoiesis.…”

Section: Jak/stat Signaling and Erythropoiesismentioning

confidence: 99%

Signaling networks guiding erythropoiesis

Kuttikrishnan,

Prabhu,

Khan

et al. 2024

Current Opinion in Hematology

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Purpose of review Cytokine-mediated signaling pathways, including JAK/STAT, PI3K/AKT, and Ras/MAPK pathways, play an important role in the process of erythropoiesis. These pathways are involved in the survival, proliferation, and differentiation function of erythropoiesis. Recent findings The JAK/STAT pathway controls erythroid progenitor differentiation, proliferation, and survival. The PI3K/AKT signaling cascade facilitates erythroid progenitor survival, proliferation, and final differentiation. During erythroid maturation, MAPK, triggered by EPO, suppresses myeloid genes, while PI3K is essential for differentiation. Pro-inflammatory cytokines activate signaling pathways that can alter erythropoiesis like EPOR-triggered signaling, including survival, differentiation, and proliferation. Summary A comprehensive understanding of signaling networks is crucial for the formulation of treatment approaches for hematologic disorders. Further investigation is required to fully understand the mechanisms and interactions of these signaling pathways in erythropoiesis.

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“…STAT5 is a regulator that determines lineage commitment between erythroid and megakaryocytic cell fates (88). Starting with erythroid development, EPO induces the activation of the STAT5/ JAK2 pathway (89)(90)(91)(92)(93). After activation, STAT5 interacts with the transcription factors TAL1, GATA1, and KLF1 (called "master regulators"), and the resulting complex binds enhancers of specifics genes that induce erythroid differentiation (93-96) (Figure 3).…”

Section: Role Of Stat5 Proteins During Hematopoiesismentioning

confidence: 99%

STAT5b: A master regulator of key biological pathways

2023

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The Signal Transducer and Activator of Transcription (STAT)-5 proteins are required in immune regulation and homeostasis and play a crucial role in the development and function of several hematopoietic cells. STAT5b activation is involved in the expression of genes that participate in cell development, proliferation, and survival. STAT5a and STAT5b are paralogs and only human mutations in STAT5B have been identified leading to immune dysregulation and hematopoietic malignant transformation. The inactivating STAT5B mutations cause impaired post-natal growth, recurrent infections and immune dysregulation, whereas gain of function somatic mutations cause dysregulated allergic inflammation. These mutations are rare, and they are associated with a wide spectrum of clinical manifestations which provide a disease model elucidating the biological mechanism of STAT5 by studying the consequences of perturbations in STAT5 activity. Further, the use of Jak inhibitors as therapy for a variety of autoimmune and malignant disorders has increased substantially heading relevant lessons for the consequences of Jak/STAT immunomodulation from the human model. This review summarizes the biology of the STAT5 proteins, human disease associate with molecular defects in STAT5b, and the connection between aberrant activation of STAT5b and the development of certain cancers.

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STAT5 as a Key Protein of Erythropoietin Signalization

Cited by 33 publications

References 100 publications

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19

Signaling networks guiding erythropoiesis

STAT5b: A master regulator of key biological pathways

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