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

Michael E. Engel, Maureen A. McDonnell, Brian K. Law, Harold L. Moses
1999 Journal of Biological Chemistry  
SMAD and JNK cascades are essential components of the transforming growth factor-␤ (TGF-␤) signaling machinery and are implicated in common transcriptional responses. However, the relationship of these pathways to one another downstream of the TGF-␤ receptor complex is unknown. We show that JNK is rapidly activated by TGF-␤ in a SMAD-independent manner and phosphorylates Smad3 outside its -SSXS motif. Smad3 phosphorylation by JNK facilitates both its activation by the TGF-␤ receptor complex and
more » ... its nuclear accumulation. JNK regulates SMAD-and TGF-␤-mediated transcriptional responses, yet JNK activators only partially stimulate transcriptional responses characteristic of TGF-␤ without coincident SMAD pathway activation. These results suggest an interdependent relationship between the JNK and SMAD pathways in TGF-␤-mediated transcription.
doi:10.1074/jbc.274.52.37413 pmid:10601313 fatcat:omkmcqux7vcgjaxvloqrm3sbrm