JNK regulates autocrine expression of TGF-beta1.
The c-Jun NH2-terminal kinase (JNK) has been implicated in the function of transforming growth factor beta (TGF-beta). To test the role of JNK, we examined the effect of compound disruption of the murine genes that encode the ubiquitously expressed isoforms of JNK (Jnk1 and Jnk2). We report that JNK-deficient fibroblasts isolated from Jnk1-/- Jnk2-/- mice constitutively express TGF-beta1. Complementation studies demonstrate that JNK is a repressor of Tgf-beta1 gene expression. This mechanism of regulation of TGF-beta1 expression by JNK represents an unexpected form of cross-talk between two important signaling pathways. Together, these data demonstrate that the JNK pathway may contribute to the regulation of autocrine TGF-beta1-mediated biological responses in vivo.
Ventura
Juan-Jose
JJ
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605, USA.
Kennedy
Norman J
NJ
Flavell
Richard A
RA
Davis
Roger J
RJ
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors / Q000235:genetics; D000818:Animals; D019898:Autocrine Communication; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D002455:Cell Division; D002465:Cell Movement; D024202:Electrophoretic Mobility Shift Assay; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006720:Homozygote; D048031:JNK Mitogen-Activated Protein Kinases; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases; D020239:Receptor Cross-Talk; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000235:genetics; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1; D014945:Wound Healing
D018125:Receptors, Transforming Growth Factor beta; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D001973:Bromodeoxyuridine