The building blocks of most signal transduction pathways are pairs of enzymes, such as kinases and phosphatases, that control the activity of pro-tein targets by covalent modification. It has previously been shown [Gold-beter A & Koshland DE (1981)Proc Natl Acad Sci USA78, 6840–6844] that these systems can be highly sensitive to changes in stimuli if their cata-lysing enzymes are saturated with their target protein substrates.