JIP1 scaffold protein 과 JNK isoforms의 선택적 작용 조절 기전 연구

초록

Activation of c-Jun N-terminal (JNK) is associated with a wide range of disparate cellular response to extracellular stimuli. Molecular cloning of the JNKs revealed major three isoforms (JNK1, JNK2 and JNK3) of three genes comprising the human JNK family. Here we demonstrated that the extent of the degree of activation of the three JNK isoforms in retinoic acid (RA)-induced neural differentiation or in UV- or H2O2-induced cell death. In this study, we showed that the neural differentiation of RA-treated cells induced an activation of JNK1, but not of JNK2 and JNK3. On the contrary, all three JNK isoforms were induced by UV or H2O2 treatment. In SH-SY5Y cell line overexpressing a splicing form of JIP1, a scaffold protein for JNK signaling pathway, JNK1 induction by RA-induced differentiation was inhibited. In the same cell line, JNK1 activation was also suppressed after UV and H2O2 treatment. On the contrary, JNK3 activation was inhibited by H2O2 treatment but not by UV treatment. Thereby, the activation of JNK isoforms by various stimuli was differentially regulated by JIP1. These results suggest that the activation of JNK isoforms as well as the interaction with JIP1 are different depending on the various stimulus. Futhermore, suppression of JNKs activation by the overexpression of JIP1 appears to be stimulus dependent.