Role of p38 and JNK mitogen-activated protein kinases in the activation of ternary complex factors
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Biochemistry and Molecular Biology
Document Type
Journal ArticlePublication Date
1997-05-01Keywords
3T3 CellsAnimals
CHO Cells
Calcium-Calmodulin-Dependent Protein Kinases
inhibitors
Cricetinae
DNA-Binding Proteins
Enzyme Activation
Enzyme Inhibitors
GTP-Binding Proteins*GTPase-Activating ProteinsGene Expression Regulation, EnzymologicGenes, fosInterleukin-1JNK Mitogen-Activated Protein KinasesMacromolecular SubstancesMice*Mitogen-Activated Protein KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSignal TransductionTranscription FactorsTranscription, Geneticets-Domain Protein Elk-1p38 Mitogen-Activated Protein KinasesLife SciencesMedicine and Health Sciences
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Show full item recordAbstract
The transcription factors Elk-1 and SAP-1 bind together with serum response factor to the serum response element present in the c-fos promoter and mediate increased gene expression. The ERK, JNK, and p38 groups of mitogen-activated protein (MAP) kinases phosphorylate and activate Elk-1 in response to a variety of extracellular stimuli. In contrast, SAP-1 is activated by ERK and p38 MAP kinases but not by JNK. The proinflammatory cytokine interleukin-1 (IL-1) activates JNK and p38 MAP kinases and induces the transcriptional activity of Elk-1 and SAP-1. These effects of IL-1 appear to be mediated by Rho family GTPases. To examine the relative roles of the JNK and p38 MAP kinase pathways, we examined the effects of IL-1 on CHO and NIH 3T3 cells. Studies of NIH 3T3 cells demonstrated that both the JNK and p38 MAP kinases are required for IL-1-stimulated Elk-1 transcriptional activity, while only p38 MAP kinase contributes to IL-1-induced activation of SAP-1. In contrast, studies of CHO cells demonstrated that JNK (but not the p38 MAP kinase) is required for IL-1-stimulated Elk-1-dependent gene expression and that neither JNK nor p38 MAP kinase is required for IL-1 signaling to SAP-1. We conclude that (i) distinct MAP kinase signal transduction pathways mediate IL-1 signaling to ternary complex transcription factors (TCFs) in different cell types and (ii) individual TCFs show different responses to the JNK and p38 signaling pathways. The differential utilization of TCF proteins and MAP kinase signaling pathways represents a potential mechanism for the determination of cell-type-specific responses to extracellular stimuli.Source
Mol Cell Biol. 1997 May;17(5):2360-71.Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38586PubMed ID
9111305Related Resources
Link to Article in PubMedCollections
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