TI - In TGF-beta responsive C2C12 cells , the cooperativity of Smad2 and 4 with GAL4-MEF2A and GAL4-MEF2C is ligand and receptor sensitive . . AB - In order to determine whether ligand -activated TGF-beta receptors can regulate the effects of the Smads on GAL4-MEF2 activity , C2C12 cells were co-transfected with either wild-type TGF-beta receptors or a dominant negative TGF-beta receptor (Fig 2A-D) . The dominant negative receptor , TbetaRII (K277R) , contains a substitution of lysine for arginine in its ATP -binding site and is still able to form a ligand -bound heterotetramer receptor complex but is unable to PHOSphorylate TbetaR-I ( 80 ) . The enhancement of GAL4-MEF2 activity by Smad2/4 was found to be increased by the over-expression of TGF-beta receptor complexes and was negated by expression of a dominant negative receptor , TbetaRII (K277R) ( Fig 2A and C ) . It was also found that exogenous TGF-beta -activated receptors and Smad2/4 increased the activities of both GAL4-MEF2A and GAL4-MEF2C . Alternatively , TGF-beta -activated wild-type receptors in combination with Smad3 and 4 , repressed the activity of GAL4-MEF2A and GAL4-MEF2C ( Fig 2B and D ) .