| To explore the potential role of LAR in RET tyrosine kinase activity and RET induced signal transduction , we cotransfected LAR and RET with a MEN2A or MEN2B mutation ( designated RET MEN2A or RET MEN2B ) into the NIH 3T3 cell line . ^^^ Here we show that LAR reduces the constitutive tyrosine autophosphorylation and kinase activity of RET MEN2A but not RET MEN2B , accompanying a significant decrease of phosphorylation of phospholipase Cgamma , AKT , and ERK1 / 2 . ^^^ Interestingly , LAR expression significantly decreased the levels of disulfide linked RET MEN2A dimerization . ^^^ Moreover , reduced oncogenic activity of RET MEN2A by overexpression of LAR was observed both by an in vitro colony formation assay and by in vivo tumorigenicity in scid mice . ^^^ These results thus suggest that LAR may contribute to deactivation of the RET MEN2A mutant protein and reduction of its oncogenic activity in vivo . . ^^^ |