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Curr Opin Immunol. 2011 Jun;23(3):324-9. doi: 10.1016/j.coi.2011.01.005. Epub 2011 Feb 14.

The signaling tool box for tyrosine-based costimulation of lymphocytes.

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Georg August University of Göttingen, Institute of Cellular and Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany.


Triggering lymphocyte effector functions is controlled by a diverse array of immune cell coreceptors that dampen or potentiate the primary activation signal from antigen receptors. Attenuation of lymphocyte activation has been shown to be accomplished by immunoreceptor tyrosine-based inhibition motifs that upon phosphorylation recruit protein or lipid phosphatases. By contrast, a general concept of signal amplification and/or diversification is still out. However, the recent discovery of antigen receptor-intrinsic costimulation by membrane-bound immunoglobulins in class-switched memory B cells identified a consensus phosphorylation motif that can boost antigen-induced signal chains and is also employed by costimulatory receptors on T and Natural Killer cells to provide secondary signals for cellular activation. Here we define a common basis of tyrosine-based lymphocyte costimulation comprising immunoglobulin tail tyrosine (ITT)-like phosphorylation motifs and their proximal effectors, growth factor receptor-bound protein (Grb) 2 and phosphatidylinositol-3 kinase (PI3K) enzymes of class IA.

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