ACTIVATION OF A DROSOPHILA-JANUS-KINASE (JAK) CAUSES HEMATOPOIETIC NEOPLASIA AND DEVELOPMENTAL DEFECTS
ACTIVATION OF A DROSOPHILA-JANUS-KINASE (JAK) CAUSES HEMATOPOIETIC NEOPLASIA AND DEVELOPMENTAL DEFECTS
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DOI：
10.1002/j.1460-2075.1995.tb07285.x
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发表时间：
1995-06-15
期刊：
影响因子：
11.4
通讯作者：
PERRIMON, N
中科院分区：
文献类型：
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作者：
HARRISON, DA;BINARI, R;PERRIMON, N
在哺乳动物中，许多细胞因子和生长因子刺激Janus激酶（JAK）家族的成员传递用于各种细胞类型（特别是造血谱系）的增殖和分化的信号。果蝇hopscotch（hop）基因（其编码JAK）中的突变也引起增殖缺陷。功能丧失等位基因导致幼虫的二倍体组织的致死和增殖不足。显性功能获得等位基因肿瘤致死（hop（Tum-1））导致黑色素瘤的形成和幼虫淋巴腺（造血器官）的肥大。我们发现，一个单一的氨基酸变化，啤酒花与啤酒花（Tum-1）突变。野生型啤酒花或啤酒花（Tum-1）在幼虫淋巴腺中的过表达导致与原始啤酒花（Tum-1）突变难以区分的黑色素瘤和淋巴腺肥大。此外，啤酒花在幼虫的其他组织中的过表达导致成虫的模式缺陷或致死。最后，在果蝇细胞培养物中过表达啤酒花或啤酒花（Tum-1）导致啤酒花蛋白的酪氨酸磷酸化，然而，啤酒花（Tum-1）的过表达导致比野生型的过表达更大的磷酸化。我们的结论是，啤酒花（Tum-1）编码一个过度活跃的啤酒花激酶和过度活跃的啤酒花在淋巴腺引起恶性肿瘤的果蝇血细胞。
In mammals, many cytokines and growth factors stimulate members of the Janus kinase (JAK) family to transduce signals for the proliferation and differentiation of various cell types, particularly in hematopoietic lineages. Mutations in the Drosophila hopscotch (hop) gene, which encodes a JAK, also cause proliferative defects, Loss-of-function alleles result in lethality and underproliferation of diploid tissues of the larva, A dominant gain-of-function allele, Tumorous-lethal (hop(Tum-l)), leads to formation of melanotic tumors and hypertrophy of the larval lymph glands, the hematopoietic organs. We show that a single amino acid change in Hop is associated with the hop(Tum-l) mutation. Overexpression of either wild-type hop or hop(Tum-l) in the larval lymph glands causes melanotic tumors and lymph gland hypertrophy indistinguishable from the original hop(Tum-l) mutation, In addition, overexpression of Hop in other tissues of the larva leads to pattern defects in the adult or to lethality. Finally, overexpression of either hop or hop(Tum-l) in Drosophila cell culture results in tyrosine phosphorylation of Hop protein, However, overexpression of hop(Tum-l) results in greater phosphorylation than overexpression of the wild-type. We conclude that hop(Tum-l) encodes a hyperactive Hop kinase and that overactivity of Hop in lymph glands causes malignant neoplasia of Drosophila blood cells.