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Sci. STKE, 13 March 2007
Vol. 2007, Issue 377, p. re2
[DOI: 10.1126/stke.3772007re2]


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

Clare L. Abram and Clifford A. Lowell*

Department of Laboratory Medicine, University of California, San Francisco, CA 94143, USA.

Gloss: 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.

*Corresponding author. E-mail, Clifford.Lowell{at}

Citation: C. L. Abram, C. A. Lowell, The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells. Sci. STKE 2007, re2 (2007).

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Blood 121, 1858-1867
   Abstract »    Full Text »    PDF »
ITAM-Coupled Receptors Inhibit IFNAR Signaling and Alter Macrophage Responses to TLR4 and Listeria monocytogenes.
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   Abstract »    Full Text »    PDF »
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Science Signaling 4, pe20
   Abstract »    Full Text »    PDF »
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J. Immunol. 186, 1656-1665
   Abstract »    Full Text »    PDF »
ITAM signaling in dendritic cells controls T helper cell priming by regulating MHC class II recycling.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 16 December 2008.
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Science Signaling 1, pc14
   Abstract »    Full Text »
Identification of Fc{gamma}RIIa as the ITAM-bearing receptor mediating {alpha}IIb{beta}3 outside-in integrin signaling in human platelets.
B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. Newman (2008)
Blood 112, 2780-2786
   Abstract »    Full Text »    PDF »
An ITAM-signaling pathway controls cross-presentation of particulate but not soluble antigens in dendritic cells.
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   Abstract »    Full Text »    PDF »

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