Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice.
Journal:
Science 2002 AugAuthors:
Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, Pearce W, Meek SE, Salpekar A, Waterfield MD, Smith AJ, Vanhaesebroeck B
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
...[more] 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.[less]
Mesh Headings:
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