Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.

ABSTRACT: Dnm2^fl/fl Pf4-Cre (Dnm2^Plt-/- ) mice lacking the endocytic GTPase dynamin 2 (DNM2) in platelets and megakaryocytes (MKs) develop hallmarks of myelofibrosis. At the cellular level, the tyrosine kinase JAK2 is constitutively active but decreased in expression in Dnm2^Plt-/- platelets. Additionally, Dnm2^Plt-/- platelets cannot endocytose the thrombopoietin (TPO) receptor Mpl, leading to elevated circulating TPO levels. Here, we assessed whether the hyperproliferative phenotype of Dnm2^Plt-/- mice was due to JAK2 constitutive activation or to elevated circulating TPO levels. In unstimulated Dnm2^Plt-/- platelets, STAT3 and, to a lower extent, STAT5 were phosphorylated, but their phosphoryla

SUBMITTER: Eaton N 

PROVIDER: S-EPMC9468709 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature