In concert with the research of Dr. Singer, I have been studying the regulation of CaM Kinase II in intact smooth muscle tissue. CaM Kinase II is a ubiquitous enzyme that is activated when levels of Ca2+ in the cell are increased as would happen when the cell is stimulated with a hormone or neurotransmitter. There are, however, other regulatory mechanisms in addition to calcium that control CaM Kinase II activity. Some of these have been demonstrated in in vitro situations but have not been shown in intact cells or tissues. My work has been focused on exploring these secondary regulatory pathways in intact smooth muscle cells. My studies have shown that in addition to Ca2+ -mediated activation, CaM Kinase II can be regulated through an autophosphorylation process, intracellular translocation, and association with intracellular structures. In addition to this research, I am being funded by the American Heart Association to investigate the regulation of sarcoendoplasmic reticulum (SER) function by CaM Kinase II. The SER in smooth muscle is an intracellular organelle that is the main storage site for Ca2+ within the cell. Through its capacity to take up and release Ca2+, it is the predominant regulator of intracellular Ca2+ dynamics. Although many of the factors that regulate SER function are known, there are several lines of evidence that suggest the participation of CaM Kinase II in this regulation. The nature and degree of CaM Kinase II involvement in SER function is poorly understood and is the focus of my research project.