MIT researchers have discovered that phase separation — the process by which proteins self-assemble into dense droplets inside cells — plays a critical role in regulating kinase enzymes. Condensing into droplets boosts kinase activity by increasing local enzyme concentration and attracting high levels of ATP, enabling faster phosphorylation reactions. In some cases, droplet formation also changes which targets a kinase phosphorylates, activating different signaling pathways. The study focused on three kinases: FAK, Mst2, and Abl. Notably, overexpression of FAK in cancer cells can trigger droplet formation that keeps pro-growth signals permanently active, potentially driving metastasis. A machine-learning model predicted that roughly 45% of the ~500 human kinases could form such droplets. These findings open new avenues for drug design — drugs that localize to these droplets could reduce off-target effects and more precisely inhibit cancer-related kinase activity.
