Our laboratory is interested in the signaling pathways downstream of ras that are involved in the regulation of expression of actin-binding proteins such as tropomyosin (TM) that have been shown to affect the growth and metastatic potential of tumor cells. We have shown that the expression of TM-2 is suppressed by oncogenic ras through a pathway that involves Raf, but not MEK. To further clarify the specific pathway involved, we are assessing the effects of various dominant negative fibroblasts and epithelial cells. Our laboratory is also interested in the factors that regulate the expression of the leukocyte adhesion molecule L-selection. Unlike most adhesion molecules, L-selectin is shed from the cell surface in response to leukocyte activation or exposure to L-selectin ligands. Ligand-induced shedding appears to be mediated by a protease distinct from the recently characterized ADAMS family member TACE (TNF-Alpha Converting Enzyme), which is responsible for the shedding of L-selectin in response to leukocyte activation. We are currently investigating the signaling pathways activated by encountering L-selectin ligands.