Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties

In addition to preventing crosstalk among related signaling pathways, scaff old proteins might facilitate signal transduction by preforming multimolecu lar complexes that can be rapidly activated by incoming signal. In many cas es, such as mitogen-activated protein kinase (MAPK) cascades, scaffold prot eins are necessary for full activation of a signaling pathway. To date, how ever, no detailed biochemical model of scaffold action has been suggested. Here we describe a quantitative computer model of MAPK cascade with a gener ic scaffold protein. Analysis of this model reveals that formation of scaff old-kinase complexes can be used effectively to regulate the specificity, e fficiency, and amplitude of signal propagation. In particular, for any gene ric scaffold there exists a concentration value optimal for signal amplitud e. The location of the optimum is determined by the concentrations of the k inases rather than their binding constants and in this way is scaffold inde pendent. This effect and the alteration of threshold properties of the sign al propagation at high scaffold concentrations might alter local signaling properties at different subcellular compartments. Different scaffold levels and types might then confer specialized properties to tune evolutionarily conserved signaling modules to specific cellular contexts.