Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


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.

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.

*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).

Read the Full Text

Cooperative integrin/ITAM signaling in platelets enhances thrombus formation in vitro and in vivo.
H. Zhi, L. Rauova, V. Hayes, C. Gao, B. Boylan, D. K. Newman, S. E. McKenzie, B. C. Cooley, M. Poncz, and P. J. Newman (2013)
Blood 121, 1858-1867
   Abstract »    Full Text »    PDF »
ITAM-Coupled Receptors Inhibit IFNAR Signaling and Alter Macrophage Responses to TLR4 and Listeria monocytogenes.
L. Huynh, L. Wang, C. Shi, K.-H. Park-Min, and L. B. Ivashkiv (2012)
J. Immunol. 188, 3447-3457
   Abstract »    Full Text »    PDF »
How ITAMs Inhibit Signaling.
L. B. Ivashkiv (2011)
Science Signaling 4, pe20
   Abstract »    Full Text »    PDF »
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 »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882