TAOK1 is an upstream activator of Mark. TAOK1 phosphorylated Mark on a threonine within its activation loop. In brain, TAOK1 also phosphorylated a fraction of Mark on a nearby serine, and this phosphorylation inhibited Mark activity. In cells, TAOK1 activity enhanced microtubule dynamics through activation of Mark and led to phosphorylation and detachment of microtubule-associated proteins from microtubules. TAOK1 also activated JNK in vitro. Overexpression of TAOK1 in a human nonsmall cell lung carcinoma cell line induced apoptotic morphologic changes, including cell contraction, membrane blebbing, and apoptotic body formation. Apoptotic stimuli increased the catalytic activity of endogenous TAOK1 and JNK, and dominant-negative JNK or JNK inhibition blocked the apoptotic morphologic responses to TAOK1. TAOK1 also stimulated cleavage and activation of ROCK1 by caspases, leading to cell contraction and membrane blebbing. TAOK1 was itself a substrate for caspase-3. TAOK1 is indeed involved in the execution phase of apoptosis.