Cells respond to their environment by migration towards or away from signals, adhesion to their surroundings, proliferation or cell death, and reinforcement of their skeletal structure to withstand mechanical stresses. These signals and responses are highly regulated in normal cells, but certain controls may be lost in transformed cells, such as metastatic cancer cells. We are investigating how cells receive information, process it, and respond appropriately. Since many proteins are involved in these activities, we are determining how particular protein interactions contribute to the responses. One particular protein of interest, zyxin, binds many other proteins and probably works as a scaffolding protein to bring proteins together at the appropriate time and place. We have recently shown that zyxin contributes to cell migration and actin dynamics (Hoffman et al., 2006). The normal actin cytoskeletal reinforcement that follows mechanical stimulation is also influenced by zyxin (Yoshigi et al., 2005). In addition, zyxin is one of several proteins that move between integrin-based adhesion sites at the cell membrane and the nucleus (Hervy et al., 2006). We are currently pursuing studies to characterize the role of zyxin and its many binding partners in cell adhesion, migration, and cytoskeletal reinforcement.