The effects of erythropoietin are mediated via the erythropoietin receptor. The envelope protein of Friend leukemia virus, gp55, specifically binds the Epo receptor in an infected erythroblast and activates constitutive Epo receptor signaling. Two similar gp55s, FVA and FVP, induce differences in erythroid proliferation and transformation in vivo. FVP gp55 induces polycythemia during the first stage of Friend erythroleukemia which is Epo-independent, whereas FVA gp55 induces an anemia that is Epo-dependent. During stage II of Friend disease, subsequent genetic alterations develop, resulting in an emergence of malignant erythroblasts and frank erythroleukemia.
The specific aims of this proposal are: 1) to identify and compare FVP- and FVA-induced changes in Epo receptor-mediated signaling and relate these changes to their differential growth and transformation properties; and 2) to compare structure/function effects of FVA and FVP mutants on Epo receptor binding and activation of erythropoietin receptor signaling, and relate these to changes in growth and transformation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA074317-03
Application #
2895963
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Cole, John S
Project Start
1997-04-11
Project End
1999-08-31
Budget Start
1999-04-01
Budget End
1999-08-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115