Stimulus-dependent Differential Regulation of JNK1 and JNK3 by JIP1 Scaffold Protein in Human Neuroblastoma, SH-SY5Y / 대한해부학회지

ABSTRACT

Activation of c-Jun N-terminal kinase (JNK) is associated with a wide range of disparate cellular responses to extracellular stimuli. In mammals, three JNK isoforms are known, and their differential regulation occurs in a stimulus- or a cell type-dependent manner. However, the underlying mechanism of this differential regulation has not been clearly elucidated. Here we demonstrated that JNK1 and JNK3 were activated in SH-SY5Y cells after treatment with H2O2 or UV. In SH-SY5Y cells overexpressing mJIP1, a splicing variant of a JNK scaffold protein JIP1, the H2O2-induced activities of both JNK1 and JNK3 were significantly suppressed. In the same cell line, however, UV-induced JNK1 activity was significantly suppressed, but JNK3 activity was not. During the RA-induced differentiation of SH-SY5Y cells, JNK1 was activated, whereas JNK3 was not, and this JNK1 activation was completely abolished in the cells overexpressing mJIP1. These results suggest that JIP1 plays a role in the regulation of the isoform-specific activation of JNKs in stimulus-dependent manner.