The goal of this Program Project is to understand cell signaling as a three dimensional process, organized and expedited by an array of cytoskeletal structures, receptor complexes, adapter proteins and targeting molecules. The Program Project aims to understand how molecular signals are propagated in "Time and Space" using several well characterized cellular systems as experimental paradigms. It seeks to integrate new experimental approaches, innovative technology and well characterized Cell systems to gain new insights into how signals are generated at/or within defined cellular Compartments, the temporal nature of these signals and how such signals are "read out" to yield information that drives cell movement, movement of cellular organelles and progression through the cell cycle. The spatial and temporal analysis of signal transduction is fundamental to understanding normal cellular regulation and critical to understanding abnormal cellular signaling processes, central hallmarks of cancer cells. The next Project ( T. Parsons) seeks to understand how signal transduction cascades initiated by extracellular matrix-integrin interactions regulate cell adhesion, cell motility, cell growth and differentiation. The next Project (D.Brautigan) will study the role of myosin phosphatase in the regulation of cell migration, particularly the regulated control of actomyosin motor activity by the phosphorylation and dephosphorylation of the regulatory light chain. The next Project (I. Macara) will study the functions of TC10, a small GTPase related to Cdc42 and Rac, and of several new effectors for TC10 and Cdc42. The next Project (J. Garrison) studies the role of G- protein-gamma-y-subunits in the signaling to phosphatidylinositol 3- kinase. The next Project (S. Parsons) investigates the role of c-Src and related kinases and tyrosine phosphatases in the regulation of the secretory process in chromaffin cells at or immediately downstream of the nicotinic acetylcholine receptor. The next Project ( M. Weber) proposes to utilize a molecular engineering methodology to identify direct substrates of the Mitogen Activated Protein Kinase, ERK2. The Protein Production Core will provide large quantities of protein reagents for biochemical studies. The Cellular Imaging Core will provide instrumentation and data analysis capability to support the study of cell movement and intracellular signaling in single cells.