Signalling to suit function: tailoring phosphoinositide 3-kinase during T-cell activation

• Published in: Trends in immunology Vol. 28; no. 4; pp. 161 - 168
• Main Authors: Parry, Richard V, Riley, James L, Ward, Stephen G
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2007; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Humans; Immune system; Kinases; Ligands; Lymphocyte Activation - immunology; Lymphocytes; Phosphatidylinositol 3-Kinases - physiology; Phosphorylation; Proteins; Receptor Cross-Talk - immunology; Regulation; Signal Transduction - immunology; Signal Transduction - physiology; T cell receptors; T-Lymphocyte Subsets - enzymology; T-Lymphocyte Subsets - immunology
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2007.02.004

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.