title: The p85beta regulatory subunit of phosphoinositide 3-kinase has unique and redundant functions in B cells.
abstract: Phosphoinositide kinase (PI3K) is activated by various receptors on lymphocytes and regulates development, activation, and tolerance. Genetic ablation of PI3K function in T cells leads to the appearance of autoimmune disorders. In B cells, loss of the class IA regulatory subunit p85alpha causes a partial defect in B cell development and proliferation, whereas loss of p85beta alone causes no apparent changes in B cell function. Here we investigate further the consequences of p85beta deletion in B cells, in the presence or absence of p85alpha. We demonstrate that p85beta partially compensates for loss of p85alpha in B cell development and peripheral survival, with greater defects observed when both isoforms are absent. BCR-mediated AKT phosphorylation is partially reduced in p85alpha-deficient B cells and further diminished with concomitant loss of p85beta. Unexpectedly, loss of p85beta results in increased BCR-mediated proliferation and ERK phosphorylation. These results indicate that the p85beta regulatory isoform has partially overlapping functions with p85alpha in B cells as well as a unique role in opposing BCR responses.
authors.affiliation: Department of Molecular Biology and Biochemistry, and Center Institute for Immunology, University of California, Irvine, Irvine, CA 92697-3900, USA.
authors.forename: Jean S
authors.initials: JS
authors.lastname: Oak
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Raechel Q
authors.initials: RQ
authors.lastname: Peralta
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Deane
authors.forename: David A
authors.initials: DA
authors.lastname: Fruman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology*; D002454:Cell Differentiation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases