Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1
Activation of RhoA and SAPK/JNK signalling pathways by the RhoA-specific exchange factor mNET1
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DOI：
10.1093/emboj/17.14.4075
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发表时间：
1998-07-15
期刊：
影响因子：
11.4
通讯作者：
Treisman, R
中科院分区：
文献类型：
--
作者：
Alberts, AS;Treisman, R
我们已经鉴定了DH结构域蛋白mNET1，一个rho家族鸟嘌呤核苷酸交换因子（GEF）。mNET1的N端截断会产生活化的蛋白转化形式mNET1 δ N，它作为RhoA的GEF，而不是Cdc42或Rac1。在NIH 3T3细胞中，活化的mNET1诱导肌动蛋白应激纤维的形成并增强转录因子血清反应因子的活性，抑制剂研究表明，这些过程依赖于RhoA，不依赖于Cdc42或Rac1，与gtpase缺陷的RhoA相反。然而，V14突变体中活化的mNET1的表达也激活了SAPK/JNK通路。这需要mNET1 GEF活性，因为它被mNET1 DH结构域及其c端pleckstrin同源（PH）结构域的点突变和显性干扰RhoA突变体RhoA阻断。虽然mNET1 δ n诱导的SAPK/JNK激活需要C3转移酶敏感的GTPase，但它独立于可滴定的gtp结合RhoA的产生而发生，因此，mNET1除了激活RhoA直接控制的信号通路外，还可以激活信号通路。
We have characterized the DH domain protein mNET1, a Rho-family guanine nucleotide exchange factor (GEF). N-terminal truncation of mNET1 generates an activated transforming form of the protein, mNET1 Delta N, which acts as a GEF for RhoA but not Cdc42 or Rac1. In NIH 3T3 cells, activated mNET1 induces formation of actin stress fibres and potentiates activity of the transcription factor serum response factor, Inhibitor studies show that these processes are dependent on RhoA and independent of Cdc42 or Rac1, In contrast to the GTPase-deficient RhoA.V14 mutant, however, expression of activated mNET1 also activates the SAPK/JNK pathway. This requires mNET1 GEF activity, since it is blocked by point mutations in the mNET1 DH domain and its C-terminal pleckstrin homology (PH) domain, and by the dominant-interfering RhoA mutant RhoA.N19, Although mNET1 Delta N-induced SAPK/JNK activation requires a C3 transferase-sensitive GTPase, it occurs independently of the generation of titratable GTP-bound RhoA, Thus, mNET1 can activate signalling pathways in addition to those directly controlled by activated RhoA.