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Sci. STKE, 13 March 2007
Vol. 2007, Issue 377, p. re2
[DOI: 10.1126/stke.3772007re2]
REVIEWS
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.
Abstract:
The immunoreceptor tyrosine-based activation motif (ITAM) is the primary signaling domain used by classical immunoreceptors, such as the antigen receptors on B and T lymphocytes and the Fc receptors (FcRs) on myeloid cells. The ITAM is contained in the intracellular region of subunits associated with these receptors, often in pairs, or is part of the cytoplasmic domain of the receptors themselves. Data from many investigators have demonstrated that ITAMs are both necessary and sufficient for initiation of signaling downstream of all immunoreceptors. More recent reports indicate that ITAM signaling is used by additional receptors beyond the classical immunoreceptors: Cell adhesion molecules (integrins and PSGL-1), chemokine receptors (CXCR4), plexins, and lectin receptors all mediate immune cell function through ITAM-like signaling pathways. This convergence of intracellular signaling pathways in leukocytes illuminates the importance of tyrosine-based activation motifs in the immune system and suggests that inhibitors of ITAM signaling may have broader effects than originally envisioned.
Pyk2 Is Required for Neutrophil Degranulation and Host Defense Responses to Bacterial Infection.
L. A. Kamen, J. Schlessinger, and C. A. Lowell (2011)
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.
D. B. Graham, H. M. Akilesh, G. B. Gmyrek, L. Piccio, S. Gilfillan, J. Sim, R. Belizaire, J. A. Carrero, Y. Wang, G. S. Blaufuss, et al. (2010)
Blood
116, 3208-3218
|Abstract »|Full Text »|PDF »
Calcium-Activated Pathways and Oxidative Burst Mediate Zymosan-Induced Signaling and IL-10 Production in Human Macrophages.
E. K. Kelly, L. Wang, and L. B. Ivashkiv (2010)
J. Immunol.
184, 5545-5552
|Abstract »|Full Text »|PDF »
In vivo Cytotoxicity of Type I CD20 Antibodies Critically Depends on Fc Receptor ITAM Signaling.
S. de Haij, J. H. M. Jansen, P. Boross, F. J. Beurskens, J. E. Bakema, D. L. Bos, A. Martens, J. S. Verbeek, P. W. H. I. Parren, J. G. J. van de Winkel, et al. (2010)
Cancer Res.
70, 3209-3217
|Abstract »|Full Text »|PDF »
Tumor Progression Locus 2 (Map3k8) Is Critical for Host Defense against Listeria monocytogenes and IL-1{beta} Production.
L. A. Mielke, K. L. Elkins, L. Wei, R. Starr, P. N. Tsichlis, J. J. O'Shea, and W. T. Watford (2009)
J. Immunol.
183, 7984-7993
|Abstract »|Full Text »|PDF »
Integrins in immunity.
R. Evans, I. Patzak, L. Svensson, K. De Filippo, K. Jones, A. McDowall, and N. Hogg (2009)
J. Cell Sci.
122, 215-225
|Abstract »|Full Text »|PDF »
Science Signaling Podcast: 16 December 2008.
J. F. Foley and A. M. VanHook (2008)
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.
D. B. Graham, L. M. Stephenson, S. K. Lam, K. Brim, H. M. Lee, J. Bautista, S. Gilfillan, S. Akilesh, K. Fujikawa, and W. Swat (2007)
J. Exp. Med.
204, 2889-2897
|Abstract »|Full Text »|PDF »
