Interdependent SMAD and JNK Signaling in Transforming Growth Factor-β-mediated Transcription

来自 Semantic Scholar

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105

作者：

ME Engel，MA Mcdonnell，BK Law，HL Moses

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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.

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关键词：

Cells, Cultured rhoA GTP-Binding Protein Mitogen-Activated Protein Kinase Kinases MAP Kinase Kinase 4 Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 3 JNK Mitogen-Activated Protein Kinases Transforming Growth Factor beta Plasminogen Activator Inhibitor 1 DNA-Binding Proteins