Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization

Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):13023-7. doi: 10.1073/pnas.91.26.13023.

Abstract

Thrombopoietin (TPO), a lineage-specific cytokine affecting the proliferation and maturation of megakaryocytes from committed progenitor cells, is believed to be the major physiological regulator of circulating platelet levels. Recently we have isolated a cDNA encoding a ligand for the murine c-mpl protooncogene and shown it to be TPO. By employing a murine cDNA probe, we have isolated a gene encoding human TPO from a human genomic library. The TPO locus spans over 6 kb and has a structure similar to that of the erythropoietin gene (EPO). Southern blot analysis of human genomic DNA reveals a hybridization pattern consistent with a single gene locus. The locus was mapped by in situ hybridization of metaphase chromosome preparations to chromosome 3q26-27, a site where a number of chromosomal abnormalities associated with thrombocythemia in cases of acute myeloid leukemia have been mapped. A human TPO cDNA was isolated by PCR from kidney mRNA. The cDNA encodes a protein with 80% identity to previously described murine TPO and is capable of initiating a proliferative signal to murine interleukin 3-dependent BaF3 cells expressing the murine or human TPO receptor.

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Chromosomes, Human, Pair 3
  • DNA Primers / chemistry
  • DNA, Complementary / genetics
  • Gene Expression
  • Genes
  • Humans
  • In Situ Hybridization, Fluorescence
  • Megakaryocytes / cytology
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / genetics
  • Receptors, Cytokine*
  • Receptors, Immunologic / metabolism
  • Receptors, Thrombopoietin
  • Recombinant Proteins
  • Thrombopoietin / genetics*
  • Thrombopoietin / pharmacology

Substances

  • DNA Primers
  • DNA, Complementary
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Receptors, Cytokine
  • Receptors, Immunologic
  • Receptors, Thrombopoietin
  • Recombinant Proteins
  • MPL protein, human
  • Thrombopoietin

Associated data

  • GENBANK/L36051
  • GENBANK/L36052