Covalent modification of proteins as a threshold mechanism in development.

Thresholds are a central but somewhat neglected aspect of cellular processes in development. An analysis has been made of the conditions in which different thresholds can be generated in the covalent modification of a number of target proteins when the concentration of an effector is continuously increased. It is assumed that the effector, which could represent a morphogen, activates, for example, kinases that phosphorylate the proteins. Thresholds are found when the modifying enzymes are saturated by their protein substrates, i.e. in conditions of zero-order ultrasensitivity (Goldbeter, A. & Koshland, D. E. 1981. An amplified sensitivity arising from covalent modification in biological systems. Proc. natn. Acad. Sci. U.S.A. 78, 6840-6844). Sequential thresholds can be generated when the kinase/phosphatase pairs differ either in the ratio of maximum modification rates or in the affinity of the effector for each kinase.