Phosphoinositide 3-kinase in T cell activation and survival.
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 p110delta 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-X(L). 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.
Okkenhaug
K
K
Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, Babraham Institute, Cambridge CB2 4AT, U.K. klaus.okkenhaug@bbsrc.ac.uk
Bilancio
A
A
Emery
J L
JL
Vanhaesebroeck
B
B
D000818:Animals; D018106:CD28 Antigens / Q000737:chemistry; D002455:Cell Division; D002470:Cell Survival; D058534:Class I Phosphatidylinositol 3-Kinases; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology*; D051020:bcl-X Protein
D018106:CD28 Antigens; D058534:Class I Phosphatidylinositol 3-Kinases; D016207:Cytokines; D007376:Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D019707:Receptors, Chemokine; D051020:bcl-X Protein; C494811:BCL2L1 protein, human; C421683:Pik3cd protein, mouse