Interdependent SMAD and JNK signaling in transforming growth factor-β-mediated transcription

被引：454

作者：

Engel, ME

McDonnell, MA

Law, BK

Moses, HL

机构：

[1] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Sch Med, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 1999年 / 274卷 / 52期

关键词：

D O I：

10.1074/jbc.274.52.37413

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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.

引用

页码：37413 / 37420

页数：8

共 34 条

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[2]

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