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

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 1999 Dec 22

PMID 10601313

Citations 177

Authors

M E Engel

M A McDonnell

B K Law

H L Moses

Affiliations

Soon will be listed here.

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.

Citing Articles

Broadening horizons: molecular mechanisms and disease implications of endothelial-to-mesenchymal transition.

Qian C, Dong G, Yang C, Zheng W, Zhong C, Shen Q Cell Commun Signal. 2025; 23(1):16.

PMID: 39789529 PMC: 11720945. DOI: 10.1186/s12964-025-02028-y.

SIRT1 Activation Suppresses Corneal Endothelial-Mesenchymal Transition via the TGF-β/Smad2/3 Pathway.

Yu Y, Guo R, Ling J, Xu C, Ma M, Dong X Curr Issues Mol Biol. 2024; 46(12):13846-13859.

PMID: 39727955 PMC: 11727023. DOI: 10.3390/cimb46120827.

Y-27632 targeting ROCK1&2 modulates cell growth, fibrosis and epithelial-mesenchymal transition in hyperplastic prostate by inhibiting β-catenin pathway.

Shan S, Su M, Wang H, Guo F, Li Y, Zhou Y Mol Biomed. 2024; 5(1):52.

PMID: 39455522 PMC: 11511810. DOI: 10.1186/s43556-024-00216-9.

LMTK2 switches on canonical TGF-β1 signaling in human bronchial epithelial cells.

Cruz D, Donovan J, Hejenkowska E, Mu F, Banerjee I, Kohn M Am J Physiol Lung Cell Mol Physiol. 2024; 327(5):L769-L782.

PMID: 39316683 PMC: 11560069. DOI: 10.1152/ajplung.00034.2024.

Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells.

Akkiz H, Gieseler R, Canbay A Int J Mol Sci. 2024; 25(14).

PMID: 39063116 PMC: 11277292. DOI: 10.3390/ijms25147873.