PI3Ks (phosphoinositide 3-kinases) regulate diverse signalling pathways involved in growth, proliferation, survival, differentiation and metabolism. In T cells, PI3Ks can be activated by a number of different receptors, including the TcR (T cell receptor), co-stimulatory receptors, cytokine receptors and chemokine receptors. However, the specific roles of PI3Ks downstream of these receptors vary. An inactivating mutation in the leucocyte-specific PI3K isoform p110 δ results in impaired TcR-dependent proliferation under circumstances where CD28 co-stimulation is blocked or not required. Recruitment and activation of PI3K by CD28 promotes survival by inducing increased expression of Bcl-XL. However, CD28 engages additional signals that regulate proliferation and interleukin-2 production independently of PI3K. Thus a model emerges whereby PI3K is involved in both TcR and CD28 signalling, but each receptor may only exploit a subset of the signalling pathways potentially controlled by PI3K activation.
- p110 Δ
- phosphoinositide 3-kinase (PI3K)
- T cell receptor
PI-3 Kinase in Signalling and Disease, a Biochemical Society Focused Meeting held at Novartis Horsham Research Centre, U.K., 11–12 November 2003
Abbreviations used: APC, antigen-presenting cell; GEF, guanine nucleotide exchange factor; LAT, linker for activation of T cells; PI3K, phosphoinositide 3-kinase; PKB, protein kinase B; PLC, phospholipase C; Pten, phosphatase and tensin homologue deleted on chromosome 10; SH2, Src homology 2; TcR, T cell receptor; TRIM, TcR-interacting molecule.
- © 2004 Biochemical Society