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

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...

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Veröffentlicht in:The Journal of biological chemistry 1999-12, Vol.274 (52), p.37413-37420
Hauptverfasser: Engel, M E, McDonnell, M A, Law, B K, Moses, H L
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container_end_page 37420
container_issue 52
container_start_page 37413
container_title The Journal of biological chemistry
container_volume 274
creator Engel, M E
McDonnell, M A
Law, B K
Moses, H L
description 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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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Cells, Cultured
DNA-Binding Proteins - physiology
JNK Mitogen-Activated Protein Kinases
MAP Kinase Kinase 4
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase Kinases - physiology
Mitogen-Activated Protein Kinases - physiology
Phosphorylation
Plasminogen Activator Inhibitor 1 - biosynthesis
rhoA GTP-Binding Protein - physiology
Smad2 Protein
Smad3 Protein
Trans-Activators - physiology
Transcription, Genetic - drug effects
Transforming Growth Factor beta - pharmacology
transforming growth factor-b
title Interdependent SMAD and JNK signaling in transforming growth factor-beta-mediated transcription
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