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-mediated Signaling
(Received for publication, November 6, 1996)
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From Transforming growth factor 
INSERM U 55, Institut Fédératif de
Recherche du Centre Hospitalo-Universitaire Saint-Antoine,
Hôpital Saint-Antoine, 184 Rue du Faubourg Saint-Antoine,
75571, Paris Cedex 12, France and the ¶ Program in Molecular
Medicine, Department of Biochemistry and Molecular Biology, University
of Massachusetts Medical School and Howard Hughes Medical Institute,
Worcester, Massachusetts 01605
(TGF-) is a
multifunctional factor that induces a wide variety of cellular
processes which affect growth and differentiation. TGF- exerts its
effects through a heteromeric complex between two transmembrane
serine/threonine kinase receptors, the type I and type II receptors.
However, the intracellular signaling pathways through which TGF-
receptors act to generate cellular responses remain largely undefined.
Here, we report that TGF- initiates a signaling cascade leading to stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activation. Expression of dominant-interfering forms of various components of the SAPK/JNK signaling pathways including Rho-like GTPases, mitogen-activated protein kinase (MAPK) kinase kinase 1 (MEKK1), MAPK kinase 4 (MKK4), SAPK/JNK, and c-Jun abolishes TGF--mediated signaling. Therefore, the SAPK/JNK activation
contributes to TGF- signaling.
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