ROLE OF P38 AND JNK MITOGEN-ACTIVATED PROTEIN-KINASES IN THE ACTIVATION OF TERNARY COMPLEX FACTORS

The transcription factors Elk-l and SAP-I bind together with serum res ponse factor to the serum response element present in the c-fos promot er and mediate increased gene expression. The ERK, JNK, and p38 groups of mitogen-activated protein (MAP) kinases phosphorylate and activate Elk-l 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 pro inflammatory cytokine interleukin-l (IL-1) activates JNK and p38 MAP k inases and induces the transcriptional activity of Elk-l and SAP-1. Th ese effects of IL-I appear to be mediated by Rho family GTPases. To ex amine the relative roles of the JNK and p38 MAP kinase pathways, we ex amined the effects of IL-1 on CHO and NIH 3T3 cells. Studies of NIH 3T 3 cells demonstrated that both the JNK and p38 MAP kinases are require d for IL-l-stimulated Elk-l transcriptional activity, while only p38 M AP kinase contributes to IL-1-induced activation of SAP-1. In contrast , studies of CHO cells demonstrated that JNK (but not the p38 MAP kina se) is required for IL-l-stimulated Elk-l-dependent gene expression an d that neither JNK nor p38 MAP kinase is required for IL-1 signaling t o SAP-1. We conclude that (i) distinct MAP kinase signal transduction pathways mediate IL-I signaling to ternary complex: transcription fact ors (TCFs) in different cell types and (ii) individual TCFs show diffe rent responses to the JNK and p38 signaling pathways. The differential utilization of TCF proteins and MAP kinase signaling pathways represe nts a potential mechanism for the determination of cell-type-specific responses to extracellular stimuli.