INVOLVEMENT OF CRAF1, A RELATIVE OF TRAF, IN CD40 SIGNALING

CD40 is a receptor on the surface of B lymphocytes, the activation of which leads to B cell survival, growth, and differentiation. A yeast t wo-hybrid screen identified a gene, CRAF1, encoding a protein that int eracts directly with the CD40 cytoplasmic tail through a region of sim ilarity to the tumor necrosis factor-alpha (TNF-alpha) receptor-associ ated factors. Overexpression of a truncated CRAF1 gene inhibited CD40- mediated up-regulation of CD23. A region of CRAF1 was similar to the T NF-alpha receptor-associated factors TRAF1 and TRAF2 and so defined a shared TRAF-C domain that was necessary and sufficient for CD40 bindin g and homodimerization. The CRAF1 sequence also predicted a long amphi pathic helix, a pattern of five zinc fingers, and a zinc ring finger. It is likely that other members of the TNF receptor superfamily use CR AF-related proteins in their signal transduction processes.