NEITHER ERK NOR JNK SAPK MAP KINASE SUBTYPES ARE ESSENTIAL FOR HISTONE H3/HMG-14 PHOSPHORYLATION OR C-FOS AND C-JUN INDUCTION/

The effects of EGF, TPA, UV radiation, okadaic acid and anisomycin on ERK and JNK/SAPK MAP kinase cascades have been compared with their abi lity to elicit histone H3/HMG-14 phosphorylation and induce c-fos and c-jun in C3H 10T1/2 cells. EGF and UV radiation activate both ERKs and JNK/SAPKs but to markedly different extents; EGF activates ERKs more strongly than JNK/SAPKs, whereas UV radiation activates JNK/SAPKs much more strongly than ERKs. Anisomycin and okadaic acid activate JNK/SAP Ks but not ERKs, and conversely, TPA activates ERKs but not JNK/SAPKs. Nevertheless, all these agents elicit phosphorylation of ribosomal an d pre-ribosomal S6, histone H3 and HMG-14, and the induction of c-fos and c-juit, showing that neither cascade is absolutely essential for t hese responses, We then analysed the relationship between ERKs, JNK/SA PKs and the transcription factors Elk-1 and c-Jun, implicated in contr olling c-fos and c-jun, respectively, JNK/SAPKs bind to GST-cJun(1-79) , and ERKs, particularly ERK-2, to GST-Elk1(307-428); there is no cros s-specificity of binding. Further, GST-Elk1(307-428) binds preferentia lly to active rather than inactive ERK-2. In vitro, JNK/SAPKs phosphor ylate both GST-cJun(1-79) and GST-Elk1(307-428), whereas ERKs phosphor ylate GST-Elk1(307-428) but not GST-cJun(1-79). Thus, neither ERKs nor JNK/SAPKs are absolutely essential for nuclear signalling and c-fos a nd c-jun induction. The data suggest either that activation of a singl e MAP kinase subtype is sufficient to elicit a complete nuclear respon se, or that other uncharacterised routes exist.