In the past year, research on the cellular function of ets-1 has focused on the role of ets-1 in astrocyte signalling and differentiation. Progress has been made in three major aspects: 1) analysis of ets-1 phosphorylation in response to transmitters in primary astrocytes, 2) identification of kinase inhibitors which block ets-1 phosphorylation in vivo, and 3) characterization of the effects of ets-1 transfection on P19 cells and on retinoic acid-induced differentiation of these cells along the neuronal and astrocyte lineages. Cleveland mapping studies comparing ets-1 from primary rat astrocytes, human astrocytoma, and human T-cell lines reveal identical sets of peptides. In primary astrocytes, the transmitters glutamate and norepinephrine were found to trigger phosphorylation of ets-1. Inhibitors of myosin light chain kinase block ets-1 phosphorylation in response to agonists and Ca++ ionophore and also block the previously described hyperphosphorylation of ets-1 in mitotic cells. P19 cells transfected to constitutively express ets-1 display morphological alterations resembling early stages of retinoic acid-induced differentiation. Work is continuing in each of these areas.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CP005591-06
Application #
3752695
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
United States
Zip Code