Characterization of mpl cytoplasmic domain sequences required for myeloproliferative leukemia virus pathogenicity.
v-mpl is a truncated form of a receptor-like chain which belongs to the cytokine receptor superfamily. This sequence has been transduced in the myeloproliferative leukemia virus as an env-mpl fusion gene responsible for an acute myeloproliferative disorder in mice. We constructed a series of viral mutants in the mpl sequence. Analysis of their oncogenic potential in vivo indicated that a critical 69-amino-acid-long cytoplasmic domain of v-Mpl is required for myoproliferative leukemia virus pathogenicity. We also developed an in vitro assay and showed that expression of the env-mpl gene confers growth factor independence to murine as well as to human hematopoietic growth factor-dependent cell lines. These findings strongly suggest that v-Mpl delivers a constitutive proliferative signal through a limited region of its cytoplasmic domain.
INSERM U363, ICGM, Hôpital Cochin, Paris, France.
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Bénit
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Courtois
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Charon
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Varlet
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Dusanter-Fourt
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Gisselbrecht
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000737:chemistry; D003673:Defective Viruses / Q000235:genetics / Q000472:pathogenicity; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D015682:Retroviridae Proteins, Oncogenic / Q000737:chemistry / Q000235:genetics*
D015682:Retroviridae Proteins, Oncogenic