Mechanistic Diversity of Cytokine Receptor Signaling Across Cell Membranes

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Science's STKE  04 May 2004:
Vol. 2004, Issue 231, pp. re7
DOI: 10.1126/stke.2312004re7

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This STKE Review addresses the issue of how signals get across biological membranes to initiate signal transduction pathways inside the cell. Extracellular ligands bind to their specific membrane receptors and mediate signal transduction by two general mechanisms. In the first, "Vertical Signaling," changes in a preassembled transmembrane receptor structure are relayed to bring about changes on the other side of the membrane, and this often occurs extremely quickly. Such changes may lead to opening of ion channels, or may be detected by other proteins that are specific to a particular activated receptor structure. In the second, "Horizontal Signaling," ligand binding induces a change in the association of receptors in the plane of the membrane. This mechanism predominates in cytokine signaling, in which signaling is slower, and often leads to regulation of transcription of specific genes. We focus here on the surprising diversity in the ways horizontal signaling controls the activation state of receptor proteins.