ROLES OF FAK IN RAT CENTRAL NERVOUS SYSTEM

The objective of the proposed research is to characterize the roles of the Focal Adhesion Kinase (FAK) in rat central nervous system. Focal adhesion kinase, a 125-kDa cytoplasmic protein tyrosine kinase, localizes to focal adhesions when cells spread on a substratum. pp125(FAK) is activated by many different extracellular stimuli in many proliferative or oncogenic cells, e.g., extracellular matrix proteins, growth factors, neuropeptides, and lysophosphatidic acid (LPA). In addition to these extracellular stimuli, there is a stable association of FAK with pp60(src) in src transformed cells, and FAK may be one of the substrates of v-src. pp125(FAK) appears to play important roles in regulating signalling events initiated by the interactions of different extracellular stimuli and membrane-cytoskeleton proteins. Furthermore, in addition to functions of FAK in the nervous system is not clear. The specific aims of this proposal are designed to investigate the functions of pp125(FAK) in rat brain using a combination of biochemical, molecular, and immunological techniques. To study the functions of FAK in the brain, I plan to: 1)Determine FAK expression pattern and its subcellular distribution in rat brain at different stages during development; 2) Characterize and identify the proteins that interact with FAK in rat brain; 3) Investigate the mechanisms of the activation of FAK tyrosine kinase activity in the rat brain.