Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells

Masaaki Takatoku, Minako Kametaka, Ritsuko Shimizu, Yasusada Miura, Norio Komatsu

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

To identify the functional domains of the human thrombopoietin (TPO) receptor essential for proliferation and megakaryocytic differentiation, we introduced human wild type c-mpl cDNA and deletion mutants of c-mpl cDNA into the human erythropoietin (EPO)-dependent cell line UT-7/EPO that does not express endogenous c-Mpl. TPO induced the proliferation and megakaryocytic differentiation of UT-7/EPO expressing wild type c-Mpl, as evidenced by increased levels of the CD41 antigen specific for cells of the megakaryocytic lineage and by changes in morphology. Mutational analysis of the cytoplasmic domain of c-Mpl identified four functional regions: (a) two C-terminal regions (amino acids 575-586 and 615-630) containing a domain essential for cell proliferation and megakaryocytic differentiation but not for DNA synthesis; (b) a region (amino acids 587-614) containing a negative domain for TPO-induced cell proliferation and megakaryocytic differentiation; and (c) a region (amino acids 565-574) including a box2 motif that is required for DNA synthesis. These deletion mutants will provide useful materials for analyzing the signals specific for TPO-induced proliferation and megakaryocytic differentiation.

Original languageEnglish
Pages (from-to)7259-7263
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number11
DOIs
Publication statusPublished - 1997 Mar 14

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Identification of functional domains of the human thrombopoietin receptor required for growth and differentiation of megakaryocytic cells'. Together they form a unique fingerprint.

Cite this