TI - RORgammat selectively prevents Id1 -induced p38 MAP kinase hyper-activation . AB - p38 MAP kinase is often activated in cells under stress or undergoing apoptosis [33,34] . Therefore , we measured p38 activation in Id1 and/or RORgammat expressing 16610D9 cells . Since T cell receptor ( TCR ) signaling is known to influence MAP kinase activities [35] , we also examined MAP kinase activation following TCR signaling triggered by incubation with anti-CD3 antibodies . Even in the absence of anti-CD3 , the level of phospo-p38 ( pp38 ) was dramatically increased by Id1 but not by RORgammat . RORgammat appeared to decrease the level of pp38 compared to vector control but this became insignificant when normalized against total amounts of p38 in each lane . However , co-expression of Id1 with RORgammat abolished the positive effect of Id1 on p38 activation before and after anti-CD3 stimulation (Fig 5A) . This effect of RORgammat is consistent with its anti-apoptotic function shown in Fig. 4 . However , whether p38 activation is directly regulated by RORgammat or indirectly influenced by the overall cellular condition remains to be investigated . In contrast to p38 activation , Erk1 and 2 were PHOSphorylated immediately following TCR signaling . TCR -induced activation of Erk1 and 2 was potentiated by Id1 expression , although basal levels of Erk1 and 2 present in the absence of TCR stimulation were not affected . However , RORgammat had no effect on Erk activation in the absence or presence of Id1 (Fig 5A) . Therefore , these results provided supporting evidence that RORgammat specifically counteracts Id1 -induced p38 activation . Id1 expression did not alter JNK activities with or without TCR stimulation ( data not shown ) . Therefore , the effect of RORgammat on JNK was not examined . Consistent with our findings in 16610D9 T cells , we have also detected elevated levels of PHOSphorylated p38 in double positive thymocytes freshly isolated from Id1 transgenic mice ( Fig 5B ) . Likewise , levels of activated Erk were also increased in these cells . Thus , these data indicate that Id1 expression alters MAP kinase signaling not only in T cell lines but also in thymocytes of transgenic mice .