Publication Date:
2002-07-20
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okkenhaug, Klaus -- Bilancio, Antonio -- Farjot, Geraldine -- Priddle, Helen -- Sancho, Sara -- Peskett, Emma -- Pearce, Wayne -- Meek, Stephen E -- Salpekar, Ashreena -- Waterfield, Michael D -- Smith, Andrew J H -- Vanhaesebroeck, Bart -- New York, N.Y. -- Science. 2002 Aug 9;297(5583):1031-4. Epub 2002 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12130661" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens/immunology
;
B-Lymphocytes/enzymology/*immunology
;
Bone Marrow Cells/cytology
;
Catalytic Domain
;
Cell Differentiation
;
Cell Division
;
Female
;
Gene Targeting
;
Hematopoietic Stem Cells/cytology
;
Immunoglobulins/blood
;
Inflammatory Bowel Diseases/immunology/pathology
;
Interleukin-2/biosynthesis
;
Intestinal Mucosa/pathology
;
Lymph Nodes/cytology/pathology
;
Lymphocyte Activation
;
Male
;
Mice
;
Mice, Inbred C57BL
;
Phosphatidylinositol 3-Kinases/genetics/*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/pathology
;
T-Lymphocytes/enzymology/*immunology
;
Thymus Gland/cytology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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