Activation of small GTPase Rho is required for autocrine motility factor signaling.
Activation of small GTPase Rho is required for autocrine motility factor signaling.
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发表时间：
2002-08
期刊：
影响因子：
11.2
通讯作者：
S. Tsutsumi;S. Gupta;V. Hogan;John G. Collard;A. Raz
中科院分区：
文献类型：
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作者：
S. Tsutsumi;S. Gupta;V. Hogan;John G. Collard;A. Raz
肿瘤转移的标志是细胞从最初的生长部位扩散到远处的器官。自分泌运动因子(AMF)是一种肿瘤相关的C-X-X-C细胞因子，是一种独特的78 kDa 7跨膜受体的配体，是细胞运动的有效模拟器，这一过程是肿瘤进展和转移的先决条件。由于对AMF依赖的信号转导知之甚少，我们试图研究AMF信号转导是否与Rho样GTP酶家族成员有关。AMF刺激人黑色素瘤细胞形成应力纤维，同时上调和激活RhoA和rac1的表达，而CDC42的表达水平或激活状态没有明显变化。在AMF刺激前用C3胞外酶处理细胞，既抑制了应力纤维样结构的形成，又抑制了RhoA的激活。此外，c-jun NH(2)末端激酶1和c-jun NH(2)末端激酶2同时被AMF激活，支持它们参与RhoA信号通路的观点。因此，我们得出结论，AMF信号转导途径与先前建立的旁分泌因子信号转导途径相似，涉及细胞骨架重排和小RhoA样GTP酶介导的形态改变。
The hallmark of tumor metastasis is the dissemination of cells from the primary growth site to distant organs. Autocrine motility factor (AMF), a tumor-associated C-X-X-C cytokine, the ligand for a unique 78 kDa seven transmembrane receptor, is a potent simulator of cell motility, a process that is a prerequisite for tumor progression and metastasis. Because little is known about AMF-dependent signaling, we sought to study whether AMF signaling involves family members of the Rho-like GTPases. AMF stimulation of human melanoma cells resulted in stress-fiber formation, concomitant with up-regulation and activation of both RhoA and Rac1 expression with no apparent changes in the expression level or activation state of Cdc42. Treatment of the cells with C3 exoenzyme before AMF stimulation inhibited both the formation of stress-fiber-like structures and the activation of RhoA. In addition, both c-Jun NH(2)-terminal kinase 1 and c-Jun NH(2)-terminal kinase 2 were simultaneously activated by AMF, supporting the notion that they are involved in the signaling pathway of RhoA. We thus conclude that AMF signaling shares a similar pathway to previously established paracrine factors signaling involving cytoskeletal rearrangement and morphological alterations mediated by the small RhoA-like GTPases.