The major aim of this Program Project is to understand the molecular pathways that regulate cell growth and trigger specialized cell functions and to delineate how these pathways are altered in a cancer cell. The Program Project seeks to bring together individuals with expertise in cell biology, molecular biology, virology, immunology, biochemistry and pharmacology to address problems relating directly to the molecular biology of cellular signalling. Support is requested to continue the investigation of molecular biology of the signal transduction process with emphasis on the molecular interactions of mitogen, receptors, proto-oncogene products and how these interactions serve to mediate specific events in normal and malignant cells. In Project 1, Dr. Weber will analyze the interaction of the Rous sarcoma virus src protein with the EGF receptors. The Weber laboratory will study the effects of src activity on the synthesis, stability and function of these receptors. In project 2, Dr. J.T. Parsons will study the structure and function of the viral src protein and its non-oncogenic cellular homologue, pp60c-src. The Parsons laboratory will employ a repertoire of src mutants to define the interactions of the src protein with specific targets, the regulation of pp60c-src activity by cellular factors and will attempt to elucidate the precise role of pp60c in the signal transduction pathway. Project 3 (Dr. Garrison) will address the role of G-proteins in the coupling of cellular receptors, in particular the EGF receptor, to various second messenger pathways. The Garrison laboratory will study the role of toxin sensitive G- proteins in EGF receptor mediated signalling. These studies include the identification and cloning of the G-protein genes as well as a more thorough analysis of the regulation of the hepatocyte EGF receptor. In project 4, Dr. Bender will study the molecular mechanisms that regulate the transcriptional attenuation of the c-myb gene, including the identification of specific DNA sequences involved in attenuation and specific cellular factors that actively mediate attenuation. In project 5, Drs. Creutz and S. Parsons will study role of tyrosine protein kinases in secretion an exocytosis. The functional role of the src kinase in the events leading to secretion and the role of tyrosine kinase substrates in mediating molecular events leading to membrane fusion and secretion will be analyzed.
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