B-cell activating factor-receptor specific activation of tumor necrosis factor receptor associated factor 6 and the phosphatidyl inositol 3-kinase pathway in lymphoma B cells

Frank Secreto, Michelle Manske, Tammy Price-Troska, Steven Ziesmer, Lucy S. Hodge, Stephen M. Ansell, James R. Cerhan, Anne J. Novak

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

B-cell activating factor-receptor (BAFF-R) is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF-R system, and high serum BAFF levels or genetic alterations in BAFF receptors have been found in B-cell cancers. BAFF signaling impacts pro-survival pathways. However, other than nuclear factor-κB2 (NF-κB2), little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we have demonstrated that activation of BAFF-R, independent of transmembrane activator and cytophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA), can induce phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β). Expression of an activated form of BAFF-R also enhanced a pro-survival gene expression pattern, including the novel BAFF-regulated gene Pin1, whose expression was phosphatidyl inositol 3-kinase (PI3K)-dependent. Additionally, we showed that TRAF6 is essential for mediating BAFF-R dependent activation of Akt. Together these data describe a novel role for TRAF6 in BAFF-R-specific activation of the PI3K pathway and provide evidence suggesting a new role for Pin1 in BAFF-R signaling.

Original languageEnglish (US)
Pages (from-to)1884-1892
Number of pages9
JournalLeukemia and Lymphoma
Volume55
Issue number8
DOIs
StatePublished - Aug 2014

Keywords

  • BAFF
  • BAFF-R
  • Lymphoma
  • PI3K

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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