Druillennec Sabine, Dorard Coralie, Eychène Alain
Institut Curie, 91405 Orsay, France.
J Nucleic Acids. 2012;2012:639062. doi: 10.1155/2012/639062. Epub 2011 Oct 5.
Among the 518 protein kinases encoded by the human kinome, several of them act as oncoproteins in human cancers. Like other eukaryotic genes, oncogenes encoding protein kinases are frequently subjected to alternative splicing in coding as well as noncoding sequences. In the present paper, we will illustrate how alternative splicing can significantly impact on the physiological functions of oncogenic protein kinases, as demonstrated by mouse genetic model studies. This includes examples of membrane-bound tyrosine kinases receptors (FGFR2, Ret, TrkB, ErbB4, and VEGFR) as well as cytosolic protein kinases (B-Raf). We will further discuss how regular alternative splicing events of these kinases are in some instances implicated in oncogenic processes during tumor progression (FGFR, TrkB, ErbB2, Abl, and AuroraA). Finally, we will present typical examples of aberrant splicing responsible for the deregulation of oncogenic kinases activity in cancers (AuroraB, Jak2, Kit, Met, and Ron).
在人类激酶组编码的518种蛋白激酶中，有几种在人类癌症中充当癌蛋白。与其他真核基因一样，编码蛋白激酶的癌基因在编码序列和非编码序列中经常发生可变剪接。在本文中，我们将举例说明可变剪接如何显著影响致癌蛋白激酶的生理功能，小鼠遗传模型研究已证明了这一点。这包括膜结合酪氨酸激酶受体（FGFR2、Ret、TrkB、ErbB4和VEGFR）以及胞质蛋白激酶（B-Raf）的例子。我们还将进一步讨论这些激酶的常规可变剪接事件在某些情况下如何与肿瘤进展过程中的致癌过程相关（FGFR、TrkB、ErbB2、Abl和AuroraA）。最后，我们将展示导致癌症中致癌激酶活性失调的异常剪接的典型例子（AuroraB、Jak2、Kit、Met和Ron）。
