The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells

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Science's STKE  13 Mar 2007:
Vol. 2007, Issue 377, pp. re2
DOI: 10.1126/stke.3772007re2

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Cells of the immune system express a diverse number of cell surface receptors that recognize a diverse set of stimuli. Stimulation of these receptors by exogenous molecules initiates biochemical events in the immune cell that activate its ability to kill invading pathogens, produce antibodies, or secrete inflammatory cytokines. Understanding how these intracellular signals are transmitted from the cell surface is critical for intervening when dysregulation of these pathways leads to immune dysfunction, such as in autoimmune or inflammatory diseases. Although immune cells use various receptors to recognize exogenous stimuli, current research suggests that many of these receptors engage a common downstream intracellular signaling pathway. Central to this pathway are transmembrane adapter proteins that contain a dual tyrosine-containing motif (the immunoreceptor tyrosine-based activation motif, or ITAM) in their cytoplasmic tails. This protein domain serves as a target for protein phosphorylation events by tyrosine kinases that initiate the common downstream pathway. This STKE Review, with two figures, one table, and 39 references, describes how ITAM-dependent signaling pathways are used by a broad array of cell surface receptors.