Genomic structure, chromosomal localization, and conserved alternative splice forms of thrombopoietin.
Thrombopoietin (TPO), the ligand for c-mpl, is a novel cytokine comprising an amino terminal domain with homology to erythropoietin and a glycosylated carboxyl terminal domain that does not bear overall homology to other known proteins. We report the cloning of cDNAs encoding the porcine and murine TPO and the characterization of the human TPO gene. The cDNA for an additional splice form (TPO-2) with a four-amino-acid deletion within the erythropoietin-like domain has been isolated and is conserved between humans, pigs, and mice. Species comparison of TPO shows that the amino terminal erythropoietin-like domain is highly conserved, while the carboxyl terminal domain is less conserved. Recombinant murine TPO and human TPO are each able to activate both the murine and human c-mpl receptors, indicating an absence of strict species specificity. Human TPO is encoded by a single gene consisting of six exons and located on chromosome 3q27-28.
Department of Molecular Biology, Genentech, Inc, San Francisco, CA 94080.
A L
AL
Gurney
W J
WJ
Kuang
M H
MH
Xie
B E
BE
Malloy
D L
DL
Eaton
F J
FJ
de Sauvage
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D017124:Conserved Sequence; D017931:DNA Primers; D004921:Erythropoietin / Q000235:genetics; D005091:Exons; D015698:Genomic Library; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018121:Receptors, Cytokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins / Q000494:pharmacology; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D013552:Swine; D013926:Thrombopoietin / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology
D017931:DNA Primers; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; C082218:MPL protein, human; D013926:Thrombopoietin