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

Engel ME, McDonnell MA, Law BK, Moses HL
J Biol Chem. 1999 274 (52): 37413-20

PMID: 10601313 · DOI:10.1074/jbc.274.52.37413

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.

MeSH Terms (15)

Cells, Cultured DNA-Binding Proteins JNK Mitogen-Activated Protein Kinases MAP Kinase Kinase 4 Mitogen-Activated Protein Kinase 3 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Phosphorylation Plasminogen Activator Inhibitor 1 rhoA GTP-Binding Protein Smad2 Protein Smad3 Protein Trans-Activators Transcription, Genetic Transforming Growth Factor beta

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