Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation
Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation
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DOI：
10.1074/jbc.m207127200
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发表时间：
2002-10-18
影响因子：
4.8
通讯作者：
Kinch, MS
中科院分区：
文献类型：
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作者：
Kikawa, KD;Vidale, DR;Kinch, MS
蛋白质酪氨酸磷酸化的细胞内信号通常被理解为控制细胞行为的许多方面。这种信号通路的生物学后果是重要的，因为蛋白酪氨酸磷酸化水平在癌细胞中经常升高。在经典范例中，酪氨酸激酶促进肿瘤细胞的生长、存活和侵袭性，而酪氨酸磷酸酶则对这些相同的行为起到负调控作用。在这里，我们确定了一种特殊的酪氨酸磷酸酶，低分子量酪氨酸磷酸酶（LAW-PTP），它在转化细胞中经常过表达。我们还表明，LMW-PTP的过表达足以使未转化的上皮细胞转化。值得注意的是，我们发现EphA2受体酪氨酸激酶是LMW-PTP的重要底物，而LMW-PTP的致癌活性源于EphA2表达和功能的改变。这些结果表明LMW-PTP在转化过程中的作用，并将其致癌潜能与EphA2联系起来。
Intracellular signaling by protein tyrosine phosphorylation is generally understood to govern many aspects of cellular behavior. The biological consequences of this signaling pathway are important because the levels of protein tyrosine phosphorylation are frequently elevated in cancer cells. In the classic paradigm, tyrosine kinases promote tumor cell growth, survival, and invasiveness, whereas tyrosine phosphatases negatively regulate these same behaviors. Here, we identify one particular tyrosine phosphatase, low molecular weight tyrosine phosphatase (LAW-PTP), which is frequently overexpressed in transformed cells. We also show that overexpression of LMW-PTP is sufficient to confer transformation upon non-transformed epithelial cells. Notably, we show that the EphA2 receptor tyrosine kinase is a prominent substrate for LMW-PTP and that the oncogenic activities of LMW-PTP result from altered EphA2 expression and function. These results suggest a role for LMW-PTP in transformation progression and link its oncogenic potential to EphA2.