Investigations into regulation of cell growth of several growth factors and by certain oncogenic viruses have recently converged, focusing attention on tyrosine-specific protein kinases. The binding of several polypeptide growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin, somatomedin C, and tumor growth factors to their respective cellular receptors, results in very rapid (less than 1 min) activation of a receptor-associated tyrosine kinase. The activated kinases cause rapid tyrosine phosphorylation of the respective growth-factor receptors as well as several cellular proteins. Further implicating tyrosinespecific protein kinases in the control of cell growth has been the finding that oncogenic transformation of cells by certain viruses is dependent on the presence of virally encoded tyrosine kinases. However, progress in these studies has been impeded by the extreme rarity of phosphotyrosine (PTYR)-proteins and the difficulty in distinguishing them from the 1000-fold more prevalent phosphoserine- and phosphothreonine-proteins. To facilitate these studies, a monoclonal anti-PTYR antibody that has effectively purified PTYR-proteins both from cells stimulated by growth factors and from cells transformed by certain retroviruses was prepared. Making extensive use of this unique antibody, these studies seek to determine the significance of tyrosine phosphorylation of growth-factor receptors (e.g., to determine the stoichiometry of receptor phosphorylation in vivo, and to determine whether tyrosine phosphorylation of receptors modulates receptor function), to elucidate the physiology and metabolism of phosphorylated receptors, and to begin to identify and characterize physiologically relevant PTYR-proteins. Parallel studies will probe the significance of tyrosine phosphorylation of viral-transforming proteins and will seek to characterize their physiologically relevant substrates. (J)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA039235-02
Application #
3178040
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1984-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Roger Williams Hospital
Department
Type
DUNS #
City
Providence
State
RI
Country
United States
Zip Code
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