biostudies-literatureEaton NNational Heart, Lung, and Blood InstituteNHLBI NIH HHSAmerican Society of Hematology959806https://www.ebi.ac.uk/biostudies/studies/S-EPMC9468709biostudies-literatureUnknown12<i>Dnm2^fl/fl Pf4-Cre</i> (<i>Dnm2^Plt-/-</i> ) 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 <i>Dnm2^Plt-/-</i> platelets. Additionally, <i>Dnm2^Plt-/-</i> platelets cannot endocytose the thrombopoietin (TPO) receptor Mpl, leading to elevated circulating TPO levels. Here, we assessed whether the hyperproliferative phenotype of <i>Dnm2^Plt-/-</i> mice was due to JAK2 constitutive activation or to elevated circulating TPO levels. In unstimulated <i>Dnm2^Plt-/-</i> platelets, STAT3 and, to a lower extent, STAT5 were phosphorylated, but their phosphorylaFrontiers in oncologyEndocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.PMC9468709P01 HL046925K12 HL141954P01 HL151333R01 HL126743HL046925, HL089224, HL141954, HL151333, HL126743R01 HL089224Hoffmeister KMLee-Sundlov MMBoyd EKFalet HSola-Visner MCZheng SBiswas RRamsey HEDlugi TAEaton NBurns RTfalseEndocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice.<i>Dnm2^fl/fl Pf4-Cre</i> (<i>Dnm2^Plt-/-</i> ) 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 <i>Dnm2^Plt-/-</i> platelets. Additionally, <i>Dnm2^Plt-/-</i> platelets cannot endocytose the thrombopoietin (TPO) receptor Mpl, leading to elevated circulating TPO levels. Here, we assessed whether the hyperproliferative phenotype of <i>Dnm2^Plt-/-</i> mice was due to JAK2 constitutive activation or to elevated circulating TPO levels. In unstimulated <i>Dnm2^Plt-/-</i> platelets, STAT3 and, to a lower extent, STAT5 were phosphorylated, but their phosphoryla2022-01-01T00:00:00Z20222026-04-08T11:56:08.074Z2025-02-19T03:29:19.768ZS-EPMC94687093611093610.3389/fonc.2022.959806