Investigation of abnormal cytokine signaling and the development of the drugs modulating these signaling

(1)我们先前报道了B16 F10黑色素瘤细胞系中FAKY 929 F突变体的转移性较差。在这里，我们确定了磷脂蛋白（PLP）2在该细胞系中下调，作为FAK下游的效应分子。在体外和体内研究了PLP 2诱导转移活性的原因。(2)JAK 2突变体JAK 2 V617 F具有组成性活性，可诱导裸小鼠异常增殖和肿瘤发生，并对包括顺铂在内的抗肿瘤药物表现出耐药性。研究了JAK 2 V617 F具有如此强活性的原因。我们提出了JAK 2突变组成性激活STAT 5的概念，STAT 5可增强多种转录因子和激酶，包括c-Myc、Aurora kinaseA或Pim-1/2，从而诱导体外和体内转化。

(1) We previously reported that a FAKY929F mutant in the B16F10 melanoma cell line gave poor metastasis. Here, we identified that the phospholipid protein(PLP) 2 was downregulated in this cell line, acting as an effector molecule downstream of FAK. Why PLP2 induces the metastatic activity was investigated in vitro and in vivo.(2) A JAK2 mutant, JAK2V617F was constitutively active and induced abnormal proliferation, tumorigenesis in nude mice, as well as exhibited resistance to antitumor drugs including cisplatin. The reason why JAK2V617F has such potent activities was studied. We presented a notion that JAK2 mutation constitutively activated STAT5, which enhanced various transcription factors and kinases including c-Myc, Aurora kinaseA or Pim-1/2, thus inducing transformation in vitro and in vivo.