Identification of an oncoprotein- and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain.

TLDR

c‑Jun activity is regulated by phosphorylation of serines 63 and 73 in its N‑terminal activation domain, a process stimulated by oncogenic signals and UV light. The study sought to identify a serine/threonine kinase whose activity is induced by the same stimuli that trigger c‑Jun phosphorylation. A novel 46‑kDa c‑Jun amino‑terminal kinase (JNK) binds the c‑Jun trans‑activation domain, phosphorylates serines 63 and 73, dissociates upon phosphorylation, and mutations disrupting this interaction diminish Ha‑Ras and UV responses, underscoring its regulatory role.

Abstract

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 signals that stimulate the amino-terminal phosphorylation of c-Jun. This novel c-Jun amino-terminal kinase (JNK), whose major form is 46 kD, binds to a specific region within the c-Jun trans-activation domain and phosphorylates serines 63 and 73. Phosphorylation results in dissociation 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 mechanism through which protein kinase cascades can specifically modulate the activity of distinct nuclear targets.