Bénit L, Courtois G, Charon M, Varlet P, Dusanter-Fourt I, Gisselbrecht S
INSERM U363, ICGM, Hôpital Cochin, Paris, France.
J Virol. 1994 Aug;68(8):5270-4. doi: 10.1128/JVI.68.8.5270-5274.1994.
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.
v-mpl是一种受体样链的截短形式，属于细胞因子受体超家族。该序列已在骨髓增殖性白血病病毒中作为env-mpl融合基因进行转导，该融合基因导致小鼠发生急性骨髓增殖性疾病。我们在mpl序列中构建了一系列病毒突变体。对它们在体内致癌潜力的分析表明，v-Mpl关键的69个氨基酸长的胞质结构域是骨髓增殖性白血病病毒致病性所必需的。我们还开发了一种体外检测方法，并表明env-mpl基因的表达赋予小鼠以及人类造血生长因子依赖性细胞系生长因子非依赖性。这些发现有力地表明，v-Mpl通过其胞质结构域的有限区域传递组成性增殖信号。
