Literature DB >> 10601313

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

M E Engel1, M A McDonnell, B K Law, H L Moses.   

Abstract

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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Year:  1999        PMID： 10601313     DOI： 10.1074/jbc.274.52.37413

Source DB:  PubMed          Journal:  J Biol Chem        ISSN： 0021-9258            Impact factor:   5.157


  153 in total

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