Our research focus is on the role of cytoskeletal in signal transduction in mammalian cells. Every cell has a cytoskeleton and the rigidity of this skeleton regulates cellular responses. For instance, the cytoskeleton changes shape when a cell migrates across a substrate and the cytoskeleton dissolves and reforms when a cell divides. These processes must be very sensitively regulated, but the reactions regulating cytoskeletal plasticity are poorly understood. It is well known that protein phosphorylation reactions play key roles in signal transduction. One such reaction is the phosphorylation of the cytoskeletal protein and enzyme, myosin, by a calcium/calmodulin dependent protein kinase. This reaction regulates the enzyme activity of the myosin molecule. It also regulates the ability of the myosin molecule to form filaments and the ability of myosin to associate with actin, thereby also regulating the dynamic state of the cytoskeleton. Therefore, we have focused on how myosin phosphorylation regulates cell motility and cell division. We are particularly interested in whether retroviral expression of proteins that alter the cytoskeleton are effective gene therapy approaches for treating vascular proliferative disorders.
Publications:
1. Wilson, A.K., Gorgas, G., Claypool, W.D. and de Lanerolle, P.: An increase or a decrease in myosin II phosphorylation inhibits macrophage motility. J. Cell Biology, 114:277-283, 1991.
2. Strauss, J.D., de Lanerolle, P. and Paul, R.J.: The effects of myosin kinase inhibiting peptide on contractility and myosin phosphorylation in chemically skinned smooth muscle. Am. J. Physiol., 262:C1437-1445, 1992.
3. de Lanerolle, P., Gorgas, G., Li, X. and Shluns, K.: Myosin light chain phosphorylation does not increase during yeast phagocytosis by macrophages. J. Biol. Chem., 268:16,883-16,886, 1993.
4. Obara, K., Nikcevic, G., Pestic, L., Nowak, G., Lorimer, D.D., Guerriero, V., Jr., Elson, E.E., Paul, R.J. and de Lanerolle, P. Fibroblast contractility without an increase in basal myosin light chain phosphorylation in wild type cells and cells expressing the catalytic domain of myosin light chain kinase. J. Biol. Chem., 270:18, 734-18, 737, 1995.
5. Hecht, G.A., Pestic, L., Koytsoyris, A., Tripuraneni, J., Lorimer, D., Guerriero, V. and de Lanerolle, P.: Expression of the catalytic domain of myosin light chain kinase increases paracellular permeability, submitted for publication.