The many faces of ITAMs

Innate and adaptive immune responses are regulated by receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs). The molecular basis of ITAM signaling has been extensively characterized and serves as a model for receptor-mediated signal transduction. Src family kinases ty...

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Bibliographic Details
Published in:Trends in immunology 2007-02, Vol.28 (2), p.66-73
Main Authors: Underhill, David M, Goodridge, Helen S
Format: Article
Language:English
Subjects:
Allergy and Immunology
Amino Acid Motifs
Animals
Cytokines
Genetic Variation - genetics
Humans
Immune system
Kinases
Ligands
Lymphocytes
Models, Biological
Phosphorylation
Proteins
Recruitment
Rodents
Signal Transduction
T cell receptors
Tyrosine - chemistry
Tyrosine - genetics
Tyrosine - metabolism
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Summary:Innate and adaptive immune responses are regulated by receptors that signal through immunoreceptor tyrosine-based activation motifs (ITAMs). The molecular basis of ITAM signaling has been extensively characterized and serves as a model for receptor-mediated signal transduction. Src family kinases typically phosphorylate ITAMs on dual tyrosines, which enable recruitment and activation of Syk family kinases through binding to dual SH2 domains on these kinases. Examples of ITAM-based signaling that do not conform precisely to the standard model are becoming increasingly common. ITAMs that suppress signaling under specific conditions and activate under others have been described, as have ITAM-like signaling mechanisms using nonstandard sequence motifs. Elucidating the diversity of ITAM-based signaling mechanisms will clarify how activating signals generated by ITAMs are tightly regulated and will open opportunities for specific therapeutic manipulation of ITAM-based signaling pathways.
ISSN:1471-4906
1471-4981
DOI:10.1016/j.it.2006.12.004