ZAK is a member of the MAPKKK family of signal transduction molecules and mediates gamma radiation signaling leading to cell cycle arrest. The activity of ZAK plays a role in cell cycle checkpoint regulation as well as being involved in regulating actin organization. Expression of kinase-dead ZAK in mouse fibroblasts disrupts actin stress fibers and causes morphologic changes. ZAK can activate JNK through MKK4/MKK7 and ERK5/p38-gamma via MKK3/MKK6. Expression of ZAK increases the population of cells in the G2/M phase of the cell cycle, whereas dominant-negative ZAK attenuated the G2 arrest caused by gamma radiation.
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