Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription
Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription
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DOI：
10.1074/jbc.274.52.37413
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发表时间：
1999-12-24
影响因子：
4.8
通讯作者：
Moses, HL
中科院分区：
文献类型：
--
作者：
Engel, ME;McDonnell, MA;Moses, HL
Smad和JNK级联信号通路是转化生长因子-β信号机制的重要组成部分，与常见的转录反应有关。然而，这些通路在转化生长因子-β受体复合体下游的相互关系尚不清楚。我们发现JNK可以被转化生长因子-β以一种不依赖于SMAD的方式快速激活，并在ITS-SSXS基序之外磷酸化SMAD3。JNK对Smad3的磷酸化既促进了Smad3被转化生长因子-β受体复合体激活，又促进了Smad3的核聚集。JNK调节SMAD-和转化生长因子-β介导的转录反应，但JNK激活剂仅部分刺激具有转化生长因子-β特征的转录反应，而不同时激活SMAD途径。这些结果表明，在转化生长因子-β介导的转录中，JNK和SMAD途径之间存在相互依赖的关系。
SMAD and JNK cascades are essential components of the transforming growth factor-beta (TGF-beta) signaling machinery and are implicated in common transcriptional responses. However, the relationship of these pathways to one another downstream of the TGF-beta receptor complex is unknown. We show that JNK is rapidly activated by TGF-beta in a SMAD-independent manner and phosphorylates Smad3 outside its -SSXS motif. Smad3 phosphorylation by JNK facilitates both its activation by the TGF-beta receptor complex and its nuclear accumulation. JNK regulates SMAD- and TGF-beta-mediated transcriptional responses, yet JNK activators only partially stimulate transcriptional responses characteristic of TGF-beta without coincident SMAD pathway activation. These results suggest an interdependent relationship between the JNK and SMAD pathways in TGF-beta-mediated transcription.