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 proto‐oncogene, 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.