c-Jun amino-terminal kinase (JNK) is known to be activated and play critical roles during neural and endodermal differentiation of P19 embryonic carcinoma cells. In this study we demonstrated that of the two upstream protein kinases of JNK, only MKK4 activity was substantially enhanced in the endodermally differentiating P19 cells. This enhanced activity of MKK4 stemmed from the increased expression of MKK4 and its activation by phosphorylation. Activated MKK4 and JNK were localized in both nucleus and cytoplasm of the differentiating cells, while they were localized only in the nucleus in the undifferentiated cells, suggesting multiple roles of JNK in the course of the endodermal differentiation of P19 cells.
