title: The signaling tool box for tyrosine-based costimulation of lymphocytes.
abstract: 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.
authors.affiliation: Georg August University of Göttingen, Institute of Cellular and Molecular Immunology, Humboldtallee 34, 37073 Göttingen, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Engels
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
mesh_terms: D000818:Animals; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D011971:Receptors, Immunologic / Q000276:immunology; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
chemical_list: D007136:Immunoglobulins; D011971:Receptors, Immunologic; D014443:Tyrosine