ERK5 promotes Src-induced podosome formation by limiting Rho activation.
ERK5 promotes Src-induced podosome formation by limiting Rho activation.
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ERK5通过限制RHO激活来促进SRC诱导的足体形成。
DOI：
10.1083/jcb.200801078
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发表时间：
2008-06-30
影响因子：
7.8
通讯作者：
Martin, G. Steven
中科院分区：
文献类型：
--
作者：
Schramp, Mark;Ying, Olivia;Kim, Tai Young;Martin, G. Steven
Src活性增加，通常与肿瘤发生相关，导致形成称为podosomes的侵袭性粘连。足状体的形成需要Rho家族鸟苷三磷酸酶的功能和肌动蛋白细胞骨架的重组。此外，Src诱导转化所需的基因表达的变化，部分通过激活丝裂原活化蛋白激酶（MAPK）信号通路。我们试图确定MAPK信号是否调节足体的形成。与细胞外信号调节激酶1/2（ERK 1/2）不同，ERK 5在Src转化的成纤维细胞中被组成性激活。表达v-Src的ERK 5缺陷细胞表现出RhoA活化和信号传导增加，这导致细胞收缩，不能形成足体或诱导侵袭。Rho激酶抑制剂Y27632添加到表达v-Src的ERK 5缺陷型细胞中导致细胞延伸并恢复了podosome形成。在Src转化的细胞中，ERK 5通过激活转录因子肌细胞增强因子2C诱导Rho GTP酶激活蛋白（RhoGAP）RhoGAP 7/DLC-1的表达，RhoGAP 7的表达恢复了ERK 5缺陷细胞中的podosome形成。我们的结论是，ERK 5促进Src诱导的podosome形成诱导RhoGAP 7，从而限制Rho激活。
Increased Src activity, often associated with tumorigenesis, leads to the formation of invasive adhesions termed podosomes. Podosome formation requires the function of Rho family guanosine triphosphatases and reorganization of the actin cytoskeleton. In addition, Src induces changes in gene expression required for transformation, in part by activating mitogen-activated protein kinase (MAPK) signaling pathways. We sought to determine whether MAPK signaling regulates podosome formation. Unlike extracellular signal–regulated kinase 1/2 (ERK1/2), ERK5 is constitutively activated in Src-transformed fibroblasts. ERK5-deficient cells expressing v-Src exhibited increased RhoA activation and signaling, which lead to cellular retraction and an inability to form podosomes or induce invasion. Addition of the Rho-kinase inhibitor Y27632 to ERK5-deficient cells expressing v-Src led to cellular extension and restored podosome formation. In Src-transformed cells, ERK5 induced the expression of a Rho GTPase-activating protein (RhoGAP), RhoGAP7/DLC-1, via activation of the transcription factor myocyte enhancing factor 2C, and RhoGAP7 expression restored podosome formation in ERK5-deficient cells. We conclude that ERK5 promotes Src-induced podosome formation by inducing RhoGAP7 and thereby limiting Rho activation.
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DOI：
10.1083/jcb.148.4.665
发表时间：
2000-02-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chellaiah M;Kizer N;Silva M;Alvarez U;Kwiatkowski D;Hruska KA
通讯作者：
Hruska KA
影响因子：
8
作者：
Belguise, K;Kersual, N;Chalbos, D
通讯作者：
Chalbos, D
影响因子：
3.5
作者：
Ishizaki, T;Naito, M;Narumiya, S
通讯作者：
Narumiya, S
影响因子：
4.8
作者：
Amano, M;Ito, M;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
4.8
作者：
Kamakura, S;Moriguchi, T;Nishida, E
通讯作者：
Nishida, E