title: Signalling to suit function: tailoring phosphoinositide 3-kinase during T-cell activation.
abstract: Members of the CD28 family of co-receptors are crucial determinants of the outcome of T-cell activation. These receptors interact with ligands in the B7 family and either costimulate or co-inhibit signals through antigen-specific receptors. The T-cell-costimulatory molecules CD28 and inducible costimulator recruit and activate class 1A phosphoinositide 3-kinase (PI3K). Interestingly, the co-inhibitory molecules cytotoxic T lymphocyte antigen-4 and B and T lymphocyte attenuator also interact with class 1A PI3K. However, all co-inhibitory receptors share an ability to oppose activation of the key PI3K effector protein kinase B (also known as Akt). Recent evidence suggests that distinct mechanisms exist to limit Akt activation by different co-inhibitory receptors. This article examines how differential positive or negative regulation of the PI3K-Akt signalling pathway by CD28 family receptors enables functional differences between the receptors.
authors.affiliation: Inflammatory Cell Biology Laboratory, Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. R.V.Parry@bath.ac.uk
authors.forename: Richard V
authors.initials: RV
authors.lastname: Parry
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ward
mesh_terms: D000818:Animals; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D020239:Receptor Cross-Talk / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*
chemical_list: D019869:Phosphatidylinositol 3-Kinases