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 RIS Download
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