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 Maxted Ansell, James R Cerhan, Anne J Novak

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 - 2014

Fingerprint

B-Cell Activation Factor Receptor
Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
Interleukin-4 Receptors
B-Cell Lymphoma
Phosphatidylinositols
TNF Receptor-Associated Factor 6
B-Lymphocytes
Phosphotransferases
B-Cell Maturation Antigen
Glycogen Synthase Kinase 3
Cell Survival
Phosphorylation
Ligands
Gene Expression
Serum
Genes
Neoplasms

Keywords

  • BAFF
  • BAFF-R
  • Lymphoma
  • PI3K

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research
  • Medicine(all)

Cite this

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

In: Leukemia and Lymphoma, Vol. 55, No. 8, 2014, p. 1884-1892.

Research output: Contribution to journalArticle

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