Cytokine pleiotropy and redundancy: a view from the receptor.

All cytokines, to a greater or lesser extent, exhibit pleiotropy (multiple biological actions) and redundancy (shared biological actions). The study of cytokine receptors, most of which belong to a structurally related hemopoietin domain family, has revealed that redundancy might be explained by the usage by related cytokines of a common receptor subunit usually termed the beta-subunit and a unique ligand-specific alpha-subunit. Biological pleiotropy, on the other hand, requires that cytokine receptors exert differential activities on different cells. Potentially, this could be explained by the use of different beta-subunits, unique signaling capacities of the alpha-subunit, differential signaling capacities of different regions of the receptor complex, or differential cellular machinery that responds to the same signal in different ways. An understanding in molecular detail of the protein-protein interactions involved in receptor activation may help in understanding these phenomena and in designing novel intervention strategies.