Abstract
Steady progress has been made in our understanding of the mechanisms by which intracellular signals are relayed from the cell membrane to the nucleus. One theme that has emerged from studies of several different pathways involves the integration of key signaling proteins into multiprotein complexes. Such a mechanism organizes the proper repertoire of proteins into specific signaling pathways, preventing inappropriate activation of regulatory proteins such as transcription factors or cell cycle regulators. Varying combinations of related enzymes in a complex, often in a cell-specific manner, enables the propagation of distinct cellular responses. The precise mode of regulation can take many forms. For example, cell activation can initiate recruitment of key regulatory proteins into a higher-order complex, resulting in the sequential activation of a kinase cascade. Alternatively, enzymes may already exist as part of a multiprotein complex that functions to maintain their steady-state activity and, at the same time, properly position the enzymes so as to respond to incoming signals from the cellular environment. Such complexes could be regulated through control of their subcellular localization. Higher-order complex formation is mediated, in part, by small conserved protein-protein interaction motifs, including leucine zipper, helix-loop-helix, WW, WD-40, SH2, SH3, PH, PTB, and PDZ motifs (1). Determination of the full complement of proteins comprising these signaling complexes would greatly enhance our understanding of how specificity is achieved in the regulation of cellular processes. Furthermore, the identification of one or more components comprising a multiprotein complex would enable the development of immunoaffinity purification protocols for the purification and characterization of additional unknown components within that complex.
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Mercurio, F., Young, D.B., Manning, A.M. (2000). Detection and Purification of a Multiprotein Kinase Complex from Mammalian Cells. In: Walker, J.M., Keyse, S.M. (eds) Stress Response. Methods in Molecular Biology™, vol 99. Humana Press. https://doi.org/10.1385/1-59259-054-3:109
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DOI: https://doi.org/10.1385/1-59259-054-3:109
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