The importance of this on/off switch-like function, in the context of cancer, is perhaps best illustrated by the resistance to small-molecule inhibitors caused by mutation of a gatekeeper threonine to a bulkier hydrophobic residue in the active site of the c-Abl, c-SRC, PDGFR and EGFR protein kinases [53]. The gene discussed is WEE1; the disease is cancer.