Mechanisms of MAPK signalling specificity.
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.
Bardwell
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Department of Developmental and Cell Biology, 2208 Natural Sciences I, University of California, Irvine, CA 92697-2300, USA. bardwell@uci.edu
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005656:Fungal Proteins; D008322:Mammals; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D010446:Peptide Fragments / Q000737:chemistry; D010766:Phosphorylation; D015398:Signal Transduction; D013379:Substrate Specificity; D015003:Yeasts / Q000201:enzymology / Q000502:physiology
D005656:Fungal Proteins; D010446:Peptide Fragments; D020928:Mitogen-Activated Protein Kinases