PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5
PKA-induced F-actin rearrangement requires phosphorylation of Hsp27 by the MAPKAP kinase MK5
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DOI：
10.1016/j.cellsig.2009.01.009
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Moens, Ugo
中科院分区：
文献类型：
--
作者：
Kostenko, Sergiy;Johannessen, Mona;Moens, Ugo
丝裂原活化蛋白激酶（MAPK）途径可以在f -肌动蛋白动力学中发挥作用。在特定的。p38 MAPK/MAPK活化蛋白激酶2 (MK2)/热休克蛋白27 （Hsp27）途径参与F-actin的改变。之前，我们发现MK5与PC12细胞中cAMP/cAMP依赖性蛋白激酶途径诱导的F-actin重排有关，而其他人发现Hsp27是一个良好的体外MK5底物。在这里，我们证明MK5可以在体内特异性地与Hsp27相互作用，并在细胞中诱导丝氨酸残基78和82的磷酸化。sirna介导的Hsp27蛋白水平的缺失以及非磷酸化Hsp27- 3a突变体的过表达阻止了福斯克林诱导的f -肌动蛋白重组。虽然组成型活性MK5突变体的异位表达足以诱导PC12细胞中的F-actin重排，但Hsp27-3A的共表达可以消除这一过程。我们的研究结果表明，MK5参与了hsp27控制的f -肌动蛋白动力学，以响应camp依赖性蛋白激酶途径的激活。这些发现使得MK5/Hsp27连接成为Hsp27异常磷酸化的疾病，如转移、心血管疾病、肌肉萎缩、自身免疫性皮肤病和神经病理学的假定治疗靶点。(C) 2009爱思唯尔公司版权所有。
Mitogen-activated protein kinase (MAPK) pathways can play a role in F-actin dynamics. In particular. the p38 MAPK/MAPK-activated protein kinase 2 (MK2)/heat shock protein 27 (Hsp27) pathway is involved in F-actin alternations. Previously, we showed that MK5 is implicated in F-actin rearrangement induced by the cAMP/cAMP-dependent protein kinase pathway in PC12 cells, while others found Hsp27 to be a good in vitro MK5 substrate. Here we demonstrate that MK5 can specifically interact with Hsp27 in vivo and can induce phosphorylation at serine residues 78 and 82 in cells. siRNA-mediated depletion of Hsp27 protein levels, as well as overexpression of the non-phosphorylatable Hsp27-3A mutant prevented forskolin-induced F-actin reorganization. While ectopic expression of a constitutive active MK5 mutant was sufficient to induce F-actin rearrangement in PC12 cells, co-expression of Hsp27-3A could ablate this process. Our results imply that MK5 is involved in Hsp27-controlled F-actin dynamics in response to activation of the cAMP-dependent protein kinase pathway. These findings render the MK5/Hsp27 connection into a putative therapeutic target for conditions with aberrant Hsp27 phosphorylation such as metastasis, cardiovascular diseases, muscle atrophy, autoimmune skin disease and neuropathology. (C) 2009 Elsevier Inc. All rights reserved.