Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice.
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.
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK.
Klaus
K
Okkenhaug
Antonio
A
Bilancio
Géraldine
G
Farjot
Helen
H
Priddle
Sara
S
Sancho
Emma
E
Peskett
Wayne
W
Pearce
Stephen E
SE
Meek
Ashreena
A
Salpekar
Michael D
MD
Waterfield
Andrew J H
AJ
Smith
Bart
B
Vanhaesebroeck
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology; D020134:Catalytic Domain; D002454:Cell Differentiation; D002455:Cell Division; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007136:Immunoglobulins / Q000097:blood; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000473:pathology; D007376:Interleukin-2 / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000473:pathology; D008198:Lymph Nodes / Q000166:cytology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000473:pathology; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D000941:Antigens; D058534:Class I Phosphatidylinositol 3-Kinases; D007136:Immunoglobulins; D007376:Interleukin-2; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; C421683:Pik3cd protein, mouse