Underlying the human erythrocyte membrane are a group of peripheral proteins which aggregate to form a cytoskeletal network. This network has been suggested to play an important role in the regulation of the shape, deformability, and membrane stability of the erythrocyte. The long term goal of this proposed research program is to delineate the role of protein phosphorylation in the regulation of the dynamics and assembly of the erythrocyte cytoskeletion and of the metabolic processes of human erythrocyte. A major hypothesis of this proposal is based on the notion that protein phosphorylation may represent a mechanism for the regulation of the interactions of the cytoskeletal proteins. In support of this hypothesis, we have recently shown that phosphorylation of ankyrin and protein 4.1 reduces their affinity for spectrin. Continuing efforts will be made to purify and characterize the protein kinases of human erythrocytes and to determine the roles of these kinases in the phosphorylation of erythrocyte membrane cytoskeletal proteins. The effects of phosphorylation on the interactions of the cytoskeletal proteins will be analyzed: first, on the isolated components of the cytoskeletal network; second, on the more complex Triton shell and Triton cytoskeleton; and finally, on membrane and inside-out vesicle preparations. That 2,3-diphosphoglycerate may play a role in the regulation of cytoskeletal protein interactions will also be investigated. Lastly, the possibility that the membrane-bound cytoskeletal proteins may undergo exchange with solubilized cytoskeletal proteins and that phosphorylation may facilitate this exchange will also be explored. Hopefully, these studies will provide a better understanding of the regulation and the dynamics of the erythrocyte membrane cytoskeleton.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK023045-09A2
Application #
3227225
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1979-01-01
Project End
1993-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
9
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Overall Medical
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612