Open AccessAlternative Splicing in Oncogenic Kinases: From Physiological Functions to Cancer
Author(s) -
Sabine Druillennec,
Coralie Dorard,
Alain Eychène
Publication year - 2011
Publication title -
journal of nucleic acids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.621
H-Index - 32
eISSN - 2090-021X
pISSN - 2090-0201
DOI - 10.1155/2012/639062
Subject(s) - kinome , kinase , receptor tyrosine kinase , biology , alternative splicing , rna splicing , tyrosine kinase , grb10 , mitogen activated protein kinase , sr protein , syk , computational biology , cancer research , microbiology and biotechnology , gene , genetics , signal transduction , exon , insulin receptor , rna , insulin resistance , endocrinology , insulin
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).
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