Convergence of MAP kinase pathways on the ternary complex factor Sap-1a.

The serum response element (SRE), which is pivotal for transcriptional up-regulation of the c-fos protooncogene, is constitutively occupied by a protein complex comprising the serum response factor and a ternary complex factor (TCF). Phosphorylation of the TCFs Elk-1 and Sap-1a by the ERK and JNK subclasses of MAP kinases triggers ...
c-fos transcription. We demonstrate here that Elk-1 is barely activated by a third subclass of MAP kinases (p38), most likely because the critical residues Ser383 and Ser389 are poorly phosphorylated by p38 MAP kinase. In contrast, the TCF Sap-1a is efficiently phosphorylated by p38 MAP kinase in vitro and in vivo on the homologous residues Ser381 and Ser387. Mutation of these sites to alanine severely reduces c-fos SRE-dependent transcription mediated by Sap-1a and p38 MAP kinase. Thus, Sap-1a may be an important target for mitogens, stress and apoptotic signals to elicit a nuclear response. However, signaling from p38 MAP kinase to Sap-1a or from Sap-1a to the basal transcription machinery does not occur in all cell types nor at promoters other than the c-fos SRE, which may ensure the specificity of signaling.
Mesh Terms:
Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, DNA-Binding Proteins, Genes, Reporter, Genes, fos, Humans, Kidney, Mitogen-Activated Protein Kinases, Models, Biological, Peptide Mapping, Phosphopeptides, Phosphorylation, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fos, Recombinant Fusion Proteins, Signal Transduction, Transcription Factors, Transcription, Genetic, Transfection, ets-Domain Protein Elk-1, ets-Domain Protein Elk-4, p38 Mitogen-Activated Protein Kinases
EMBO J.
Date: Apr. 01, 1997
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