Signal transduction pathways triggered in host cells by the mammalian-infective forms of T. cruzi are required for the invasion process. Specifically the second messengers Ca+2 and cAMP are known effectors of T. cruzi induced host cell signaling. The goals of this proposal are to elucidate these signaling pathways by the identification of the specific host protein factors that are involved. Host cell kinases and phosphatases will be identified and their roles in invasion and/or host cell gene expression will be characterized. The events induced by wild-type T. cruzi will be compared to those induced by a mutant strain that is defective in triggering a specific Ca+2 host cell response, required for invasion of mammalian cells. Finally, cDNA micro array hybridization will be used to identify host cell genes that are differentially expressed during T. cruzi infection.