Characterization of mpl cytoplasmic domain sequences required for myeloproliferative leukemia virus pathogenicity. |
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| Authors: | L B nit, G Courtois, M Charon, P Varlet, I Dusanter-Fourt, S Gisselbrecht |
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| Affiliation: | L Bénit, G Courtois, M Charon, P Varlet, I Dusanter-Fourt, and S Gisselbrecht |
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| Abstract: | 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. |
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