IDENTIFICATION OF AN ONCOPROTEIN-RESPONSIVE AND UV-RESPONSIVE PROTEIN-KINASE THAT BINDS AND POTENTIATES THE C-JUN ACTIVATION DOMAIN

The activity of c-Jun is regulated by phosphorylation. Various stimuli including transforming oncogenes and UV light, induce phosphorylation of serines 63 and 73 in the amino-terminal activation domain of c-Jun and thereby potentiate its trans-activation function. We identified a serine/threonine kinase whose activity is stimulated by the same sign als that stimulate the amino-terminal phosphorylation of c-Jun. This n ovel c-Jun amino-terminal kinase (JNK), whose major form is 46 kD, bin ds to a specific region within the c-Jun trans-activation domain and p hosphorylates serines 63 and 73. Phosphorylation results in dissociati on of the c-Jun-JNK complex. Mutations that disrupt the kinase-binding site attenuate the response of c-Jun to Ha-Ras and UV. Therefore the binding of JNK to c-Jun is of regulatory importance and suggests a mec hanism through which protein kinase cascades can specifically modulate the activity of distinct nuclear targets.