A balance of signaling by Rho family small GTPases RhoA, Rac1 and Cdc42 coordinates cytoskeletal morphology but not cell survival
A balance of signaling by Rho family small GTPases RhoA, Rac1 and Cdc42 coordinates cytoskeletal morphology but not cell survival
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DOI：
10.1038/sj.onc.1202262
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发表时间：
1999-01-07
期刊：
影响因子：
8
通讯作者：
Hahn, CS
中科院分区：
文献类型：
--
作者：
Moorman, JP;Luu, D;Hahn, CS
已知Rho家族GTP酶参与细胞骨架重组。我们研究了这些功能可能由Rho家族GTPase信号平衡决定的可能性。利用病毒瞬时表达RhoA、rac1、CDc42及其突变体，以及C3胞外酶，我们在正常生长条件下改变了细胞骨架组织。野生型或活性Rho家族GTP酶的过表达导致其各自的激活表型，给定的Rho家族GTP酶的显性阴性形式的过表达导致与另一Rho家族GTP酶激活一致的表型，用C，难辨毒素A处理使所有Rho家族GTP酶失活，导致多种激活表型的瞬时出现，先前我们报道Rho失活导致细胞凋亡，暗示Rho可能在细胞生存信号中发挥重要作用。然而，这种信号不受Rad或CDC42微型体表达的影响，只有Rho失活才能诱导细胞凋亡，Rho家族GTP酶似乎通过平衡信号来协调细胞骨架组织，而细胞生存则受到不同的Rho介导的信号通路的调节。
Rho family GTPases are known to be involved in cytoskeletal reorganization. We examined the possibility that these functions may be dictated by a balance of Rho family GTPase signaling. Using transient viral expression of RhoA, Rac1, Cdc42 and their mutants, as well as C3 exoenzyme, we altered cytoskeletal organization under normal growth conditions. Overexpression of wild-type or constitutively active forms of the Rho family GTPases led to their respective activation phenotypes, Overexpression of dominant negative forms of given Rho family GTPases led to a phenotype consistent with activation of the other Rho family GTPase, Treatment with C, difficile toxin A, that inactivates all Rho family GTPases, led to the transient appearance of a variety of activation phenotypes, Previously, we reported that inactivation of Rho led to induction of apoptosis, implying that Rho may play an important role in cell survival signaling. This signaling, however, is not affected by expression of tiny forms of Rad or Cdc42, and only inactivation of Rho led to induction of apoptosis, Rho family GTPases appear to coordinate cytoskeletal organization by a balance of signaling, while cell survival is regulated by :I distinct Rho-mediated signaling pathway.