Anaplastic lymphoma kinase: signalling in development and disease.
Anaplastic lymphoma kinase: signalling in development and disease.
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DOI：
10.1042/bj20090387
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发表时间：
2009-05-27
期刊：
影响因子：
--
通讯作者：
Hallberg B
中科院分区：
文献类型：
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作者：
Palmer RH;Vernersson E;Grabbe C;Hallberg B
RTK（受体酪氨酸激酶）在细胞增殖和分化中发挥重要作用。此外，当 RTK 的激酶活性通过相应基因的点突变、扩增或重排而组成型增强时，RTK 就会显示出致癌潜力。 ALK（间变性淋巴瘤激酶）RTK 最初被鉴定为 RTK 胰岛素受体亚家族的成员，在与 ALCL（间变性大细胞淋巴瘤）相关的 t(2;5) 染色体重排中被截短并与 NPM（核磷蛋白）融合时获得转化能力。迄今为止，许多导致 ALK 活性增强的染色体重排已被描述，并且与多种癌症类型有关。最近有关 NSCLC（非小细胞肺癌）中的 EML4（棘皮动物微管相关蛋白 4）-ALK 癌蛋白的报告，以及神经母细胞瘤中激活点突变的鉴定，都强调了 ALK 作为癌症药物开发的重要参与者和靶标。在本综述中，我们探讨了 ALK 在发育和疾病中的作用，并讨论了对未来的影响。
RTKs (receptor tyrosine kinases) play important roles in cellular proliferation and differentiation. In addition, RTKs reveal oncogenic potential when their kinase activities are constitutively enhanced by point mutation, amplification or rearrangement of the corresponding genes. The ALK (anaplastic lymphoma kinase) RTK was originally identified as a member of the insulin receptor subfamily of RTKs that acquires transforming capability when truncated and fused to NPM (nucleophosmin) in the t(2;5) chromosomal rearrangement associated with ALCL (anaplastic large cell lymphoma). To date, many chromosomal rearrangements leading to enhanced ALK activity have been described and are implicated in a number of cancer types. Recent reports of the EML4 (echinoderm microtubule-associated protein like 4)–ALK oncoprotein in NSCLC (non-small cell lung cancer), together with the identification of activating point mutations in neuroblastoma, have highlighted ALK as a significant player and target for drug development in cancer. In the present review we address the role of ALK in development and disease and discuss implications for the future.