Our laboratory has been interested in several aspects of signal transduction resulting from binding of polypeptide hormones to their surface receptors on cells. One major topic under study is the role of direct substrates for protein kinase C (PKC) in mediating the many cellular effects resulting from activation of this family of kinases by hormones and other agonists. We have been studying a small family of PKC substrates consisting of MARCKS and its smaller homologue, the MARCKS-like protein or MLP. Ongoing projects include structure-function studies of the protein and its mutant derivatives in two major systems, development of the mouse central nervous system, and early embryogenesis in Xenopus laevis. We are also studying gene promoter elements in these two species to determine which elements are important for the developmentally regulated, tissue-specific and cytokine-induced expression of these genes. We are investigating potential interactions of these proteins with a protease that specifically cleaves MARCKS, cathepsin B, and potential roles of these interactions in growth and metastasis of certain tumors, especially human breast cancer. Finally, we are investigating the possibility that mutations in the MARCKS and MLP genes are involved in human neural tube defects, particularly at the level of increasing a genetic predisposition to environmental causes of these defects.
