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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.

Pubmed ID: 12130661

Authors

  • Okkenhaug K
  • Bilancio A
  • Farjot G
  • Priddle H
  • Sancho S
  • Peskett E
  • Pearce W
  • Meek SE
  • Salpekar A
  • Waterfield MD
  • Smith AJ
  • Vanhaesebroeck B

Journal

Science (New York, N.Y.)

Publication Data

August 9, 2002

Associated Grants

None

Mesh Terms

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