Using Dictyostelium, we identified a pathway in which the dimeric acidic protein 14-3-3 acts genetically between microtubules, racE and myosin II to control cell shape, cortical tension, and cytokinesis. In this context, 14-3-3 requires GTP and racE for cortical association, controls the extent of microtubule-cortex interactions, and binds myosin II heavy chain, controlling its assembly into bipolar thick filaments. This study was simplified by using Dictyostelium cells, which only has one myosin II and one 14-3-3 protein. Humans have three nonmuscle myosin II proteins and seven 14-3-3s. We have expressed and purified all 10 proteins and have discovered a very diverse landscape of 14-3-3 modulation of myosin II paralogs. This area is ongoing and revealing a multitude of disease-relevant discoveries since myosin II and 14-3-3 proteins have such fundamental roles in the cell.