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

2007; Elsevier BV; Volume: 28; Issue: 4 Linguagem: Inglês

10.1016/j.it.2007.02.004

1471-4981

Richard V. Parry, James L. Riley, Stephen G. Ward,

Immune Cell Function and Interaction

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.