We now report a novel mechanism of TRAF 2 mediated signal transduction revealed by an association of TRAF 2 with sphingosine kinase ( SphK ) , a lipid kinase that is responsible for the production of sphingosine 1 phosphate . ^^^ We identified a TRAF 2 binding motif of SphK that mediated the interaction between TRAF 2 and SphK resulting in the activation of the enzyme , which in turn is required for TRAF 2 mediated activation of NF kappa B but not JNK . ^^^ In addition , by using a kinase inactive dominant negative SphK and a mutant SphK that lacks TRAF 2 binding motif we show that the interaction of TRAF 2 with SphK and subsequent activation of SphK are critical for prevention of apoptosis during TNF stimulation . ^^^ These findings show a role for SphK in the signal transduction by TRAF 2 specifically leading to activation of NF kappa B and antiapoptosis . . ^^^ |