Evidence for a role of Rho-like GTPases and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in transforming growth factor beta-mediated signaling.
Transforming growth factor beta (TGF-beta) is a multifunctional factor that induces a wide variety of cellular processes which affect growth and differentiation. TGF-beta 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-beta receptors act to generate cellular responses remain largely undefined. Here, we report that TGF-beta 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-beta-mediated signaling. Therefore, the SAPK/JNK activation contributes to TGF-beta signaling.
Atfi
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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.
Djelloul
S
S
Chastre
E
E
Davis
R
R
Gespach
C
C
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016212:Transforming Growth Factor beta; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases