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Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice
Abstract
Class IA phosphoinositide 3-kinases (PI3Ks) are a family of p85/p110 heterodimeric lipid kinases that generate second messenger signals downstream of tyrosine kinases, thereby controlling cell metabolism, growth, proliferation, differentiation, motility, and survival. Mammals express three class IA catalytic subunits: p110α, p110β, and p110δ. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110δ (p110δ D910A ) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110δ mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110δ in immunity.
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Cites
A point mutation in CD28 distinguishes proliferative signals from survival signals.
Okkenhaug, K., Wu, L., Garza, K. M., La Rose, J., Khoo, W., Odermatt, B., Mak, T. W., Ohashi, P. S., & Rottapel, R. (2001) · Nature Immunology · doi:10.1038/86327 · Cited by 210
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Cited by
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Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,721
Targeting PI3K signalling in cancer: opportunities, challenges and limitations
Engelman, J. A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2664 · Cited by 2,445
Metadata
- Authors
- Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S. E., Salpekar, A., Waterfield, M. D., Smith, A. J. H., & Vanhaesebroeck, B.
- Venue
- Science
- Published
- 2002-08-09
- Volume
- 297
- Issue
- 5583
- Pages
- 1031-1034
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2163577434
- Cited by
- 946
- References
- 1
- FWCI
- 11.23
- Type
- journal article
- Language
- en
- Open access
- closed
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- Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S. E., Salpekar, A., Waterfield, M. D., Smith, A. J. H., & Vanhaesebroeck, B. (2002). Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice. Science. https://doi.org/10.1126/science.1073560
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