Roles of TRAF6 in CD40 signaling.

CD40 provides signals crucial to the activation of antigen-presenting cells during humoral and cell-mediated immune responses. A complex cohort of proteins interacts with the cytoplasmic domain of CD40 and mediates signaling. One member of this cohort is TNF receptor associated factor six (TRAF6). TRAF6 contributes to the CD40-mediated activation of NF-kappaB, stress-activated protein kinases, and perhaps other signaling molecules. TRAF6 may have roles as an adapter molecule, an activator of mitogen-activated protein kinases, and as a repressor of certain signaling circuits. Establishing the significance and interplay of these roles will lead to a more complete understanding of mechanisms important to the CD40-mediated activation of the immune system and will reveal novel targets for the development of therapeutic agents.