C. Ducret et al., The ternary complex factor Net contains two distinct elements that mediatedifferent responses to MAP kinase signalling cascades, ONCOGENE, 19(44), 2000, pp. 5063-5072
The ternary complex factors (TCFs), Elk-1, Sap-1a and Net, are key integrat
ors of the transcriptional response to different signalling pathways. Class
ically, three MAP kinase pathways, involving ERK, JNK, and p38, transduce v
arious extracellular stimuli to the nucleus. Net is a repressor that is con
verted into an activator by Ras/ERK signalling. Net is also exported from t
he nucleus in response to stress stimuli transduced through the JNK pathway
, leading to relief from repression. Here we show that ERK and p38 bind to
the D box and that binding is required for phosphorylation of the adjacent
C-terminally located C-domain, The D box as web as the phosphorylation site
s in the C-domain (the DC element) are required for transcription activatio
n by Pas. On the other hand, JNK binds to the J box in the middle of the pr
otein, and binding is required for phosphorylation of the adjacent EXport m
otif. Both the binding and phosphorylation sites (the JEX element) are impo
rtant for Net export. In conclusion, specific targeting of Net by MAP kinas
e pathways involves two different docking sites and phosphorylation of two
different domains. These two elements, DC and JEX, mediate two distinct fun
ctional responses.