In this study , we determined the role of PP2Cbeta 1 , a major isoform of mammalian PP2C , in the TAK 1 signaling pathway , a stress activated protein kinase cascade that is activated by interleukin 1 , transforming growth factor beta , or stress . ^^^ Ectopic expression of PP2Cbeta 1 inhibited the TAK 1 mediated mitogen activated protein kinase kinase 4 c Jun amino terminal kinase and mitogen activated protein kinase kinase 6 p 38 signaling pathways . ^^^ In vitro , PP2Cbeta 1 dephosphorylated and inactivated TAK 1 . ^^^ Coimmunoprecipitation experiments indicated that PP2Cbeta 1 associates with the central region of TAK 1 . ^^^ A phosphatase negative mutant of PP2Cbeta 1 , PP2Cbeta 1 ( R / G ) , acted as a dominant negative mutant , inhibiting dephosphorylation of TAK 1 by wild type PP2Cbeta 1 in vitro . ^^^ |