Human thrombopoietin: gene structure, cDNA sequence, expression, and chromosomal localization.
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.
Foster
D C
DC
ZymoGenetics Inc., Seattle, WA 98102.
Sprecher
C A
CA
Grant
F J
FJ
Kramer
J M
JM
Kuijper
J L
JL
Holly
R D
RD
Whitmore
T E
TE
Heipel
M D
MD
Bell
L A
LA
Ching
A F
AF
D000595:Amino Acid Sequence; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3; D017931:DNA Primers / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008533:Megakaryocytes / Q000166:cytology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D013926:Thrombopoietin / Q000235:genetics* / Q000494:pharmacology
D017931:DNA Primers; D018076:DNA, Complementary; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; C082218:MPL protein, human; D013926:Thrombopoietin