Structure and transcription of the human c-mpl gene (MPL).
The human c-mpl proto-oncogene encodes a member of the cytokine receptor superfamily, expressed mainly in CD 34-positive hematopoietic progenitors and in the megakaryocytic lineage. To investigate the elements required for this tissue-specific expression, we cloned the human c-mpl gene (MPL) as well as the 5' end of the mouse gene. The human c-mpl gene contains 12 exons distributed over 17 kb of DNA. Each of the two "cytokine receptor domains" of Mpl is encoded by a set of four exons, the transmembrane domain by a single exon and the cytoplasmic domain by two exons. We also describe how three types of mRNA, encoding different proteins, are generated. The major species contains all 12 exons; mRNAs encoding a protein with a smaller cytoplasmic domain are produced by termination of the transcript within intron 10, and mRNAs encoding a putative soluble form of the c-Mpl protein lack exons 9 and 10. The promoter regions of the human and mouse genes were characterized. These promoters are GC-rich and contain putative binding sites for proteins of the Ets and GATA families. Finally, we show that a 700-bp fragment of the human c-mpl promoter is active in the HEL and K562 cell lines, which express erythroid and megakaryocytic markers, but is inactive in the nonhematopoietic HeLa cell line and the Jurkat T lymphoid cell line.
Institut National de la Santé et de la Recherche Médicale, U. 91, Hôpital Henri Mondor, Creteil, France.
V
V
Mignotte
I
I
Vigon
E
E
Boucher de Crèvecoeur
P H
PH
Roméo
V
V
Lemarchandel
S
S
Chrétien
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D007438:Introns; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000235:genetics; D053628:Receptors, Thrombopoietin; D014158:Transcription, Genetic
D018076:DNA, Complementary; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human