This project focuses on the EDR1 protein kinase of Arabidopsis. Loss-of-function mutations in EDR1 confer enhanced disease resistance to infection by powdery mildew fungus (Erysiphe cichoracearum), and enhanced leaf senescence in response to biotic and abiotic stresses. An overlap between defense responses and senescence is well-documented, but the mechanistic basis of this overlap and its biological significance are poorly understood. We are using the EDR1 protein as a molecular entry point to uncover the signaling pathways that co-regulate these processes. Our immediate goals are to identify the substrates of EDR1, and to determine what regulates EDR1 kinase activity. To accomplish these goals we are using both genetic and biochemical approaches. To date, we have shown that the EDR1 kinase domain by itself is constitutively active, and that overexpression of this domain causes a dominant-negative phenotype. This result implies that the EDR1 kinase domain may sequester a protein or protein complex required for normal EDR1 signaling. We have identified candidate members of such a complex using yeast two-hybrid approaches. We have also identified and cloned additional genes that produce edr1-like phenotypes when mutated, and are currently screening for mutations that suppress the edr1 phenotype. We expect this work to provide new insights into how program cell death is regulated in plants, and to illuminate the general mechanisms by which other kinases of this class, such as CTR1, regulate cell processes.