It takes two to tango - signalling by dimeric Raf kinases

被引：32

作者：

Baljuls, Angela ^{[1
]}

Kholodenko, Boris N. ^{[1
]}

Kolch, Walter ^{[1
,2
]}

机构：

[1] Natl Univ Ireland Univ Coll Dublin, Dublin 4, Ireland

[2] Natl Univ Ireland Univ Coll Dublin, Conway Inst Biomol & Biomed Res, Dublin 4, Ireland

来源：

MOLECULAR BIOSYSTEMS | 2013年 / 9卷 / 04期

基金：

爱尔兰科学基金会;

关键词：

B-RAF; A-RAF; PROTEIN-KINASE; WILD-TYPE; C-RAF; PARADOXICAL ACTIVATION; PHOSPHATIDIC-ACID; MEK INHIBITORS; ONCOGENIC RAS; CAUSE NOONAN;

D O I：

10.1039/c2mb25393c

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Raf kinases function downstream of Ras proteins to activate the MEK-ERK pathway which is deregulated in a large number of human cancers. Raf inhibitors are clinically highly effective for the treatment of cancer and melanoma in particular, but have unexpected side effects that include a paradoxical activation of the ERK pathway. These effects seem to be related to the heterodimerization of Raf-1 and B-Raf kinases. Here, we discuss the role of Raf dimerization as part of the physiological activation mechanism of Raf kinases, the mechanism of Raf dimerization induced by drugs, and the implications of dimerization for drug therapies targeting Raf kinases.

引用

页码：551 / 558

页数：8

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