CELL ADHESION IN BIOLOGICAL SIGNAL TRANSDUCTION

点击翻译按钮获取中文摘要

Protein Tyrosine Phosphatase Regulation of Cellular Adhesion to Extracellular Matrices. G.B. SCHNEIDER 1-2 and K. BURRIDGE2 (Depts. of Prosthodonticsl and Cell Biology2; University of North Carolina,Chapel Hill). My research involves studying cellular adhesion and intracellular signalling in fibroblast and osteoblast focal adhesions. Focal adhesions are transmembrane structures that link the extracellular matrix with the cytoskeleton. The focal adhesion contributes to the cells ability to regulate signalling pathways involved in adhesion, cell growth, and differentiation. These regulatory mechanisms are clinically relevant during wound healing following surgical interventions, in normal cell growth and differentiation, and in patterns of gene expression in tumorigenesis. These signalling pathways are important when one considers the etiological factors of many of the maxillofacial patients we treat, in patients who have experienced progressive bone loss associated with aging, or in the osseointegrative mechanisms occurring during healing and loading of implants. The overall goal of my thesis is to try and identify an enzyme within the focal adhesion that helps to regulate these signalling pathways. One potential enzyme is called a protein tyrosine phosphatase (PTP). This type of enzyme is thought to antagonizes the effects of oncogenic products generated by tyrosine kinases (PTK). I have attempted to identify one of these phosphatases by developing polyclonal antibodies to potential phosphatase antigens, including both synthetic peptides and GST-fusion proteins. Future experiments will involve using these antibodies for immunofluorescent labelling of cells, biochemical analysis such as immunoprecipitations and Western blots, and microinjection studies to evaluate the morphological and physiological response of the cell. Other studies will evaluate data generated by affinity chromatography studies, as well as a novel PTP assay. The data gathered will help us to better understand the role of PTP's in the regulation of signalling pathways involved in adhesion, differentiation, and mitogenesis within various cell types.