The objective of this proposal is to determine the ability of calpactins(p35 and p36), the substrates of protein tyrosine kinases activated upon oncogenic transformation, to alter protein glycosylation. Calpactin II has been identified as being homologous to Lipocortin I, and inhibitor of Phospholipase A2, and lipocortins have been shown to affect the glycosylation of IgE growth factors released from T cells. The hypothesis to be tested in this proposal is that the activation of protein tyrosine kinases in the early steps of oncogenic transformation induces changes in protein glycosylation related to the phosphorylation of intracellular calpactins. The effect of calpactin/lipocortin or protein glycosylation in cell culture will be determined for secreted and membrane-bound glycoproteins. Changes in oligosaccharide structures induced by calpactin/lipocortin treatment will be determined by direct biochemical analysis. Phosphorylation of endogenous calpactin II/p35 will be induced to determine its effect of protein glycosylation. Finally, the mechanism of lipocortin induction of changes in protein glycosylation will be studied. While changes in cellular protein glycosylation have been observed upon oncogenic transformation, the types of changes resulting from lipocortin treatment of cells have not been reported. This project provides a new approach to the early changes that occur at the cell surface as a result of oncogenesis. These results will provide important information about the cellular changes induced by protein tyrosine kinase activation and about the role of the calpactin/lipocortin family in the process of oncogenic transformation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA047980-03
Application #
3459082
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1990-07-01
Budget End
1991-06-30
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198