Lim kinases, regulators of actin dynamics

Lim kinases, regulators of actin dynamics
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DOI:
10.1016/j.biocel.2006.11.011
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发表时间:
2007-01-01
影响因子:
4
通讯作者:
Bernard, Ora
Bernard, Ora
中科院分区:
生物学2区
文献类型:
--
作者:
Bernard, Ora

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LIM激酶(LIMK)家族的成员,包括LIMK 1和2,是参与肌动蛋白聚合和微管分解的调节的丝氨酸蛋白激酶。它们的活性受p21激活激酶1和4以及Rho激酶激活环内苏氨酸残基的磷酸化调节。LIMK磷酸化和磷酸化肌动蛋白解聚因子ADF/cofilin,导致细胞丝状肌动蛋白的净增加。Hsp 90通过促进LIM激酶蛋白的同源二聚化和反式磷酸化来调节LIM激酶蛋白的水平。Rnf 6是一种E3泛素连接酶,负责神经元中LIMK的降解。LIMK 1的活性也是内皮细胞中微管分解所必需的。LIMK 1主要定位于粘着斑,而LIMK 2则定位于细胞质点,这表明它们可能具有不同的细胞功能。LIMK 1被证明参与癌症转移,而LIMK 2活化促进细胞周期进展。(C)2006爱思唯尔有限公司保留所有权利。
The members of the LIM kinase (LIMK) family, which include LIMK 1 and 2, are serine protein kinases involved in the regulation of actin polymerisation and microtubule disassembly. Their activity is regulated by phosphorylation of a threonine residue within the activation loop of the kinase by p21-activated kinases 1 and 4 and by Rho kinase. LIMKs phosphorylate and inactivate the actin depolymerising factors ADF/cofilin resulting in net increase in the cellular filamentous actin. Hsp90 regulates the levels of the LIM kinase proteins by promoting their homo-dimerisation and trans-phosphorylation. Rnf6 is an E3 ubiquitin ligase responsible for LIMK degradation in neurons. The activity of LIMK1 is also required for microtubule disassembly in endothelial cells. While LIMK1 localizes mainly at focal adhesions, LIMK2 is found in cytoplasmic punctae, suggesting that they may have different cellular functions. LIMK1 was shown to be involved in cancer metastasis, while LIMK2 activation promotes cells cycle progression. (C) 2006 Elsevier Ltd. All rights reserved.