The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)


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Abbreviations

Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation

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Receptor-mediated dimerization of JAK2 FERM domains is required for JAK2 activation

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Targeting JAK/STAT signalling in inflammatory skin diseases with small molecule inhibitors

Hence, a wide variety of interconnecting signals operates on HSCs. Most of these are found in a specialized microenvironment, the stem cell niche 2 , 3 , where HSCs are localized and protected from direct stressors. Such signals include conserved evolutionary pathways like the Wnt 4 , 5 , Notch 6 and bone morphogenic proteins BMP 7 cascades, but also hematopoietic cytokines, such as stem cell factor SCF and thrombopoietin TPO 8. However, under conditions where a large supply of blood cells are needed, certain inflammatory cytokines can provide signals that induce rapid proliferation and differentiation of HSCs 9.

jak-stat signaling pathway( EPO mediated)

The combined laboratories of Ross Levine and Garry Nolan have now better investigated how the common signaling molecules underneath these inflammatory cytokine-receptors regulate HSC stem cell biology under stress IFNs play a critical role in the regulation of resistance to viral infection and activation of the innate and acquired immune system through IFN-stimulated genes. IFNs also have an anti-tumor effect as the IFN regulated target genes not only inhibit viral replication and clear infected cells but can also help in attacking cancer cells.

Development - EPO-induced Jak-STAT pathway Pathway Map - PrimePCR | Life Science | Bio-Rad

Because of their ability to regulate immune responses, recombinant type I interferons have been used clinically to treat viral infections, solid tumors and hematological malignancies, including multiple myeloma. Interestingly, while on most target cells IFNs have an anti-proliferative effect growth arrest , they have an opposite effect on stem cells. Two seminal articles by Essers et al. Essers et al.

Sato et al.


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These investigators studied mice that were genetically deficient for a negative regulator of type I interferon signaling, interferon response factor 2 [IRF2 15 ]. HSCs in these mice show chronic proliferation leading to a profound stem cell defect in secondary transplantations. The very different effects of IFNs on different types of target cells, has prompted much research into the signaling pathways emanating from their receptors. Clearly the JAK tyrosine kinases are critical mediators of these effects and hence targeted mutation of these receptors has been subject of several important publications, including a recent one by Kleppe et al.

The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20) The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)
The Jak-Stat Pathway in Hematopoiesis (Molecular Biology Intelligence Unit, 20)

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