Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice

K Okkenhaug; A Bilancio; G Farjot; A Priddle; S Sancho; E Peskett; W Pearce; Stephen Meek; A Salpekar; MD Waterfield; A. J. Smith; B Vanhaesebroeck

Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice

K Okkenhaug, A Bilancio, G Farjot, A Priddle, S Sancho, E Peskett, W Pearce, Stephen Meek, A Salpekar, MD Waterfield, A. J. Smith, B Vanhaesebroeck

Royal (Dick) School of Veterinary Studies

Research output: Contribution to journal › Article › peer-review

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: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.

Original language	English
Pages (from-to)	1031-4
Number of pages	4
Journal	Science
Volume	297
Issue number	5583
Publication status	Published - Aug 2002

Keywords / Materials (for Non-textual outputs)

Animals
Antigens/immunology
B-Lymphocytes/enzymology
B-Lymphocytes/immunology
Bone Marrow Cells/cytology
Catalytic Domain
Cell Differentiation
Cell Division
Female
Gene Targeting
Hematopoietic Stem Cells/cytology
Immunoglobulins/blood
Inflammatory Bowel Diseases/immunology
Inflammatory Bowel Diseases/pathology
Interleukin-2/biosynthesis
Intestinal Mucosa/pathology
Lymph Nodes/cytology
Lymph Nodes/pathology
Lymphocyte Activation
Male
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases/genetics
Phosphatidylinositol 3-Kinases/metabolism
Point Mutation
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins/metabolism
Proto-Oncogene Proteins c-akt
Receptors, Antigen, B-Cell/metabolism
Receptors, Antigen, T-Cell/metabolism
Signal Transduction
Spleen/cytology
Spleen/pathology
T-Lymphocytes/enzymology
T-Lymphocytes/immunology
Thymus Gland/cytology

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http://www.sciencemag.org/content/297/5583/1031.full.pdf

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title = "Impaired B and T cell antigen receptor signaling in p110delta 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: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.",

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author = "K Okkenhaug and A Bilancio and G Farjot and A Priddle and S Sancho and E Peskett and W Pearce and Stephen Meek and A Salpekar and MD Waterfield and Smith, \{A. J.\} and B Vanhaesebroeck",

year = "2002",

month = aug,

language = "English",

volume = "297",

pages = "1031--4",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5583",

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TY - JOUR

T1 - Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice

AU - Okkenhaug, K

AU - Bilancio, A

AU - Farjot, G

AU - Priddle, A

AU - Sancho, S

AU - Peskett, E

AU - Pearce, W

AU - Meek, Stephen

AU - Salpekar, A

AU - Waterfield, MD

AU - Smith, A. J.

AU - Vanhaesebroeck, B

PY - 2002/8

Y1 - 2002/8

N2 - 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: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.

AB - 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: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles. Mice expressing a catalytically inactive form of p110delta (p110delta(D910A)) were generated by gene targeting. Antigen receptor signaling in B and T cells was impaired and immune responses in vivo were attenuated in p110delta mutant mice. They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity.

KW - Animals

KW - Antigens/immunology

KW - B-Lymphocytes/enzymology

KW - B-Lymphocytes/immunology

KW - Bone Marrow Cells/cytology

KW - Catalytic Domain

KW - Cell Differentiation

KW - Cell Division

KW - Female

KW - Gene Targeting

KW - Hematopoietic Stem Cells/cytology

KW - Immunoglobulins/blood

KW - Inflammatory Bowel Diseases/immunology

KW - Inflammatory Bowel Diseases/pathology

KW - Interleukin-2/biosynthesis

KW - Intestinal Mucosa/pathology

KW - Lymph Nodes/cytology

KW - Lymph Nodes/pathology

KW - Lymphocyte Activation

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Phosphatidylinositol 3-Kinases/genetics

KW - Phosphatidylinositol 3-Kinases/metabolism

KW - Point Mutation

KW - Protein-Serine-Threonine Kinases

KW - Proto-Oncogene Proteins/metabolism

KW - Proto-Oncogene Proteins c-akt

KW - Receptors, Antigen, B-Cell/metabolism

KW - Receptors, Antigen, T-Cell/metabolism

KW - Signal Transduction

KW - Spleen/cytology

KW - Spleen/pathology

KW - T-Lymphocytes/enzymology

KW - T-Lymphocytes/immunology

KW - Thymus Gland/cytology

M3 - Article

SN - 0036-8075

VL - 297

SP - 1031

EP - 1034

JO - Science

JF - Science

IS - 5583

ER -

Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice

Abstract

Keywords / Materials (for Non-textual outputs)

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