TUMOR PROGRESSION LOCUS-2 (TPL-2) ENCODES A PROTEIN-KINASE INVOLVED IN THE PROGRESSION OF RODENT T-CELL LYMPHOMAS AND IN T-CELL ACTIVATION
TUMOR PROGRESSION LOCUS-2 (TPL-2) ENCODES A PROTEIN-KINASE INVOLVED IN THE PROGRESSION OF RODENT T-CELL LYMPHOMAS AND IN T-CELL ACTIVATION
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DOI：
10.1073/pnas.90.6.2251
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发表时间：
1993-03-15
影响因子：
11.1
通讯作者：
TSICHLIS, PN
中科院分区：
文献类型：
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作者：
PATRIOTIS, C;MAKRIS, A;TSICHLIS, PN
通过从莫洛尼白血病病毒诱导的大鼠胸腺瘤2769的三个亚系之一进行前病毒标签法克隆得到的Tpl - 2基因座，定义了一个编码蛋白激酶的基因，该基因与22.5%的肿瘤进展相关。Tpl - 2主要在脾脏、胸腺、肝脏和肺中表达。前病毒整合发生在该基因的最后一个内含子中，导致一种截短的mRNA表达，这种mRNA终止于前病毒长末端重复序列，并编码一种C末端结构域改变的蛋白质。有力的证据表明这种基因变化赋予受影响的细胞克隆生长优势，这是通过以下发现提供的：在对源自肿瘤2769的所有三个亚系进行培养期间，选择出了在Tpl - 2基因座中具有独立前病毒插入的细胞。正常大鼠脾细胞暴露于刀豆蛋白A会在暴露后的前60分钟内诱导Tpl - 2表达水平升高，这表明在正常脾细胞中，Tpl - 2可能参与细胞周期从静止期到G1期的转变。
The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.