| Transient transfection of cells with constitutively active forms of the known IL 1 signaling components MyD 88 , IRAK , and TRAF 6 , or the upstream kinases MKK 6 and MKK 3 , activated p 38 MAPK . ^^^ Dominant negative RasN 17 blocked the effect of the active forms of all but MKK 3 and MKK 6 , indicating that Ras lies downstream of TRAF 6 but upstream of MKK 3 and MKK 6 on the pathway . ^^^ Furthermore , the activation of p 38 MAPK caused by overexpressing active RasVHa could not be inhibited using dominant negative mutants of MyD 88 , IRAK , or IRAK 2 , or TRAF 6 , but could be inhibited by dominant negative MKK 3 or MKK 6 . ^^^ In the same manner , the inhibitory effect of Rap on the activation of p 38 by IL 1 occurred at a point downstream of MyD 88 , IRAK , and TRAF 6 , since the activation of p 38 MAPK by these components was inhibited by overexpressing active Rap1AV12 , while neither MKK 3 nor MKK 6 were affected . ^^^ |