Hibi M, Lin A, Smeal T, Minden A, Karin M
Department of Pharmacology, University of California San Diego, School of Medicine, La Jolla 92093-0636.
Genes Dev. 1993 Nov;7(11):2135-48. doi: 10.1101/gad.7.11.2135.
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.
c-Jun的活性受磷酸化作用调控。包括转化癌基因和紫外线在内的多种刺激，可诱导c-Jun氨基末端激活域中丝氨酸63和73的磷酸化，从而增强其反式激活功能。我们鉴定出一种丝氨酸/苏氨酸激酶，其活性受刺激c-Jun氨基末端磷酸化的相同信号所刺激。这种新型的c-Jun氨基末端激酶（JNK），其主要形式为46kD，与c-Jun反式激活域内的特定区域结合，并使丝氨酸63和73磷酸化。磷酸化导致c-Jun-JNK复合物解离。破坏激酶结合位点的突变会减弱c-Jun对Ha-Ras和紫外线的反应。因此，JNK与c-Jun的结合具有重要的调节作用，并提示了一种蛋白激酶级联反应可特异性调节不同核靶标活性的机制。
