| We previously showed that active MEKK 3 is capable of stimulating calcineurin / nuclear factor of activated T cells ( NFAT ) signaling in cardiac myocytes through phosphorylation of modulatory calcineurin interacting protein 1 ( MCIP 1 ) . ^^^ However , the protein kinases that function downstream of MEKK 3 to mediate MCIP 1 phosphorylation and the mechanism of MCIP 1 mediated calcineurin regulation have not been defined . ^^^ Here , we show that MEK 5 and big MAP kinase 1 ( BMK 1 ) function downstream of MEKK 3 in a signaling cascade that induces calcineurin activity through phosphorylation of MCIP 1 . ^^^ |