Abstract
Activation of MAPKs by their upstream MAPKKs has long been thought to be a direct process with direct binding and concomitant phosphorylation of MAPKs without a need for additional regulatory molecules. In a yeast two-hybrid screen using human MKK6 as bait, we found that p150 dynactin, a component of cytoplasmic dynein motors, specifically interacts with MKK6. Although we failed to demonstrate a clear role for dynein motors, we found an indispensable role for functional microtubules in activation of the p38 MAPKs. Disruption of microtubules leads to reduce p38 MAPK activation. This reveals an unexpected requirement for microtubules in p38 MAPK activation.