The molecular mechanisms that control thrombopoiesis
Kenneth Kaushansky
Kenneth Kaushansky
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The molecular mechanisms that control thrombopoiesis

Abstract

Our understanding of thrombopoiesis — the formation of blood platelets — has improved greatly in the last decade, with the cloning and characterization of thrombopoietin, the primary regulator of this process. Thrombopoietin affects nearly all aspects of platelet production, from self-renewal and expansion of HSCs, through stimulation of the proliferation of megakaryocyte progenitor cells, to support of the maturation of these cells into platelet-producing cells. The molecular and cellular mechanisms through which thrombopoietin affects platelet production provide new insights into the interplay between intrinsic and extrinsic influences on hematopoiesis and highlight new opportunities to translate basic biology into clinical advances.

Authors

Kenneth Kaushansky

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Hematopoietic cytokine receptor architecture and mechanism of initial si...
Hematopoietic cytokine receptor architecture and mechanism of initial signaling. A stylized hematopoietic cytokine receptor is shown, depicting the 1 or 2 cytokine receptor motifs (C, Cys; WS, Trp-Ser-Xaa-Trp-Ser), the transmembrane domain, and the box1 sequence to which JAK kinases bind. Also shown are the 3 major domains of JAK kinases, the FERM domain, which binds to box1, and the kinase JH1 and regulatory JH2 domains. Finally, upon JAK activation, the site of receptor tyrosine phosphorylation is shown, which then serves as a docking site for STATs and adapter proteins (SHC or SHP2).