Frontline: The p85α isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responses

Kristen L. Hess, Amber C. Donahue, Kwan Ng, Travis I. Moore, Jean Oak, David A. Fruman

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Phosphoinositide 3-kinase (PI3K) is a ubiquitously expressed signaling enzyme that plays an integral role in development and activation of B cells. B cell receptor (BCR)-driven proliferation is completely blocked either in cells lacking the p85α regulatory isoform of PI3K or in wild-type cells treated with pharmacological PI3K inhibitors. However, the contribution of p85α to early signaling events has not been fully investigated. Here we show that B cells lacking p85α have signaling impairments that are both quantitatively and qualitatively different from those in cells treated with PI3K inhibitors. Loss of p85α results in partial reductions in Ca2+ mobilization and IκB phosphorylation, whereas ERK phosphorylation is not diminished. Moreover, although Akt phosphorylation is partially reduced, phosphorylation of several proteins downstream of Akt is preserved. These partial impairments suggest that there are other routes to PI3K activation in B cells apart from p85α-associated catalytic subunits. Notably, addition of phorbol ester restores BCR-mediated proliferation in p85α -deficient cells but not wild-type cells treated with PI3K inhibitors. These findings suggest that the primary BCR signaling defect in B cells lacking p85α is a failure to activate diacylglycerol-regulated signaling enzymes, most likely protein kinase C.

Original languageEnglish (US)
Pages (from-to)2968-2976
Number of pages9
JournalEuropean Journal of Immunology
Volume34
Issue number11
DOIs
StatePublished - Nov 1 2004
Externally publishedYes

Fingerprint

B-Lymphocyte Subsets
1-Phosphatidylinositol 4-Kinase
Protein Isoforms
B-Lymphocytes
Phosphorylation
Diglycerides
Phorbol Esters
Enzymes
Protein Kinase C
Catalytic Domain
Pharmacology

Keywords

  • B lymphocytes
  • Signal transduction
  • Spleen
  • Transgenic/knockout

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Frontline : The p85α isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responses. / Hess, Kristen L.; Donahue, Amber C.; Ng, Kwan; Moore, Travis I.; Oak, Jean; Fruman, David A.

In: European Journal of Immunology, Vol. 34, No. 11, 01.11.2004, p. 2968-2976.

Research output: Contribution to journalArticle

Hess, Kristen L. ; Donahue, Amber C. ; Ng, Kwan ; Moore, Travis I. ; Oak, Jean ; Fruman, David A. / Frontline : The p85α isoform of phosphoinositide 3-kinase is essential for a subset of B cell receptor-initiated signaling responses. In: European Journal of Immunology. 2004 ; Vol. 34, No. 11. pp. 2968-2976.
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