Mechanisms of MAPK signalling specificity

Abstract

MAPK (mitogen-activated protein kinase) signalling pathways contribute to the regulation of diverse responses, including normal and pathological aspects of cell growth, division, differentiation and death. Their ubiquity and versatility raise the issue of how they achieve specific coupling of signal with cellular response. How do the kinases in the cascade distinguish their correct substrates from the vast excess of incorrect substrates? Furthermore, how do different signals elicit distinct responses when they are transmitted by the same components? This short review highlights several mechanisms that can promote specificity in MAPK signalling, including tethering interactions between MAPKs and their substrates and regulators mediated by docking sites, feedback loops and cross-pathway regulatory circuits, and the selective activation of scaffold proteins.

Figure 1. Tethering by MAPK-docking sites

(A) Docking of MEK and MAPK during the process of MAPK activation. (B) Docking of MAPK and a substrate during substrate phosphorylation.

Figure 2. Yeast MAPK cascades that share components

The yeast mating, filamentous invasive growth and osmostress response MAPK cascades share components, yet are normally well insulated from one another. See text for details.