This is a first amended renewal of a grant, currently in its fifth year, to study the regulation and function of p42 MAP kinase. The MAP kinases are crucial components of diverse signalling cascades. In general, Dr. Weber is testing the hypothesis that specific protein:protein interactions control the upstream regulators and downstream effectors of MAP kinase cascades as well as the timing of MAP kinase activation and the cellular location of components of the cascades. The project is divided into three specific aims. In the first aim he will examine how interactions with specific MEK activators and scaffolding proteins can regulate the efficiency with which ERKs are activated and the cross-talk with other MAP kinase family members. In Aim 2 he will determine how activation of ERKs can occur during mitosis and how activation at this time in the cell cycle provides MAP kinase with a new repertoire of possible functions. In Aim 3 he will test the idea that interaction of ERKs with transcription factors regulates the translocation of ERKs to the nucleus and thus controls their ability to participate in the regulation of gene expression.