BAFF-R Specific Activation of TRAF6 and the PI3K-Pathway in Lymphoma B Cells

摘要

BAFF-R is the primary BAFF receptor that is responsible for promoting B-cell development and survival. Malignant B-cells exploit the BAFF/BAFF receptor 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 NF-κB2, little is known about the specific pathways activated by individual BAFF receptors. Using a novel BAFF-R expression model we now demonstrate that activation of BAFF-R, independent of TACI and BCMA, can induce phosphorylation of Akt and 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 PI3K-dependent. Additionally, we show 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.