The objectives of the proposed research are to determine how Ca2+/calmodulin-dependent protein kinase IV (CaMK IV) participates in Ca2+/calmodulin regulated signal transduction cascades and whether this enzyme influences development of the cells in which it is expressed. The proposed experiments will utilize transgenic mice and mice in which the CaMK IV gene has been disrupted by gene targeting. Aim 1 will assess defects in transgenic mice expressing an inactive form of CaMK IV specifically in T-cells. In Aim 2, the role of CaMK IV and its activating kinase in receptor-mediated signaling in T-cells will be examined to determine if CaMK IV is required to promote cell proliferation or to prevent cell apoptosis in response to mitogenic stimuli. In Aim 3, the consequences of disruption of the CaMK IV gene on the development of the tissues in which it is expressed will be investigated.