HUMAN THROMBOPOIETIN - GENE STRUCTURE, CDNA SEQUENCE, EXPRESSION, AND CHROMOSOMAL LOCALIZATION

被引:130
作者
FOSTER, DC [1 ]
SPRECHER, CA [1 ]
GRANT, FJ [1 ]
KRAMER, JM [1 ]
KUIJPER, JL [1 ]
HOLLY, RD [1 ]
WHITMORE, TE [1 ]
HEIPEL, MD [1 ]
BELL, LA [1 ]
CHING, AFT [1 ]
MCGRANE, V [1 ]
HART, C [1 ]
OHARA, PJ [1 ]
LOK, S [1 ]
机构
[1] ZYMOGENET INC,SEATTLE,WA 98102
关键词
D O I
10.1073/pnas.91.26.13023
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:13023 / 13027
页数:5
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