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.
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April 2004
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Conference Article|
April 01 2004
Phosphoinositide 3-kinase in T cell activation and survival
K. Okkenhaug;
K. Okkenhaug
1
*Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, Babraham Institute, Cambridge CB2 4AT, U.K.
1To whom correspondence should be addressed (e-mail klaus.okkenhaug@bbsrc.ac.uk).
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A. Bilancio;
A. Bilancio
†Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, U.K.
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J.L. Emery;
J.L. Emery
*Laboratory of Lymphocyte Signalling and Development, Molecular Immunology Programme, Babraham Institute, Cambridge CB2 4AT, U.K.
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B. Vanhaesebroeck
B. Vanhaesebroeck
†Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, U.K.
‡Department of Biochemistry & Molecular Biology, University College London, Gower Street, London WC1E 6BT, U.K.
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Publisher: Portland Press Ltd
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 Biochemical Society
2004
Biochem Soc Trans (2004) 32 (2): 332–335.
Citation
K. Okkenhaug, A. Bilancio, J.L. Emery, B. Vanhaesebroeck; Phosphoinositide 3-kinase in T cell activation and survival. Biochem Soc Trans 1 April 2004; 32 (2): 332–335. doi: https://doi.org/10.1042/bst0320332
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