TI - The p38 MAPK PHOSphorylation sites ( Ser387 , Thr293 , Thr300 ) of MEF2C are necessary for Smad2/4 cooperativity . AB - There has been evidence to suggest that there is cross-talk between TGF-beta and p38 MAPK signalling ( 51 ) . In addition , it is known that p38 MAPK PHOSphorylation of MEF2A and MEF2C TADs modulates MEF2 activity ( 73,74,76 ) . Therefore , we tested whether MEF2 mutants that are not PHOSphorylated by p38 MAPK can still cooperate with the Smads (Fig 7B) . COS cells were transfected with expression vectors for a constitutively-active TGF-beta receptor TbetaRI (T204D) , Smad2 , 3 , 4 , GAL4-MEF2C , GAL4-MEF2C (S387A) and GAL4-MEF2C (T293,300A) . The MEF2C mutations constructed by Han et al. , GAL4-MEF2C (S387A) and GAL4-MEF2C (T293,300A) , are known to bind DNA and activate transcription of GAL4 reporter genes to the same degree as wild-type GAL4-MEF2C when co-transfected with p38 MAPK ( and constitutively active MKK3 ) and ERK5/BMK1 ( and constitutively active MEK5 ) , respectively ( 74,87 ) . It was found that enhancement of GAL4-MEF2C activity by Smad2/4 only occurred if Ser387 , Thr293 and Thr300 are intact , indicating that PHOSphorylation of MEF2C by either p38 MAPK or ERK5/BMK1 is necessary for Smad-MEF2 cooperativity .