Tumor necrosis factor alpha stimulates AP-1 activity through prolonged activation of the c-Jun kinase.

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作者：

JK Westwick，C Weitzel，A Minden，M Karin，DA Brenner

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摘要：

Tumor necrosis factor alpha (TNF alpha) has multiple biological functions including the prolonged activation of the collagenase and c-jun genes, which are regulated via their AP-1 binding sites. We show that incubating human fibroblasts with TNF alpha induces prolonged activation of JNK, the c-Jun kinase, which phosphorylates the transactivation domain of c-Jun. Furthermore, an immune complex kinase assay specifically demonstrates that TNF alpha stimulates the activity of JNK1, the recently described predominant form of JNK. TNF alpha also produces a small and transient increase in extracellular signal-regulated kinase (ERK) activity and no measured increase in Raf-1 kinase activity. On the other hand, epidermal growth factor causes a prolonged activation of Raf-1 kinase and ERK activity and a smaller, more transient activation of JNK, whereas the phorbol ester phorbol 12-myristate 13-acetate causes a small stimulation of Raf-1 kinase and a pronounced stimulation of ERK activity. The activation of JNK by TNF alpha does not correlate with Raf-1 or ERK activity. The kinetics of Raf-1, ERK, and JNK induction by epidermal growth factor, phorbol 12-myristate 13-acetate, or TNF alpha indicate distinct mechanisms of activation in human fibroblasts.

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关键词：

Cells, Cultured Humans Tetradecanoylphorbol Acetate Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-raf Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 3 Tumor Necrosis Factor-alpha Proto-Oncogene Proteins c-jun Proto-Oncogene Proteins