The proposed studies will address the hypothesis that gp35 a 33-40 kD glycoprotein is a signal-transducing molecule that interacts with ligand-binding structures in order to regulate the cellular responses of NK cells and T cells.
The specific aims are: 1) to determine whether gp35 MAb are mitogenic for freshly isolated NK cells, affect the cytolytic activity of NK cells, and activate NK cells to produce cytokines; 2) to determine whether there are cell-surface molecules which are physically associated with gp35 on NK cells and T cells; 3) to determine, by generating gp35-loss mutants of RNK-16, whether gp35 is required for target cell-induced PPI turnover within RNK-16, for cytotoxicity, and for CD2-mediated signaling; and 4) to clone the gene that encodes gp35.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA052669-04
Application #
3197486
Study Section
Experimental Immunology Study Section (EI)
Project Start
1990-08-06
Project End
1995-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bell, G M; Fargnoli, J; Bolen, J B et al. (1996) The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. J Exp Med 183:169-78
Bell, G M; Dethloff, G M; Imboden, J B (1993) CD45-negative mutants of a rat natural killer cell line fail to lyse tumor target cells. J Immunol 151:3646-53
Bell, G M; Bolen, J B; Imboden, J B (1992) Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells. Mol Cell Biol 12:5548-54
Bell, G M; Seaman, W E; Niemi, E C et al. (1992) The OX-44 molecule couples to signaling pathways and is associated with CD2 on rat T lymphocytes and a natural killer cell line. J Exp Med 175:527-36
Imboden, J B; Bell, G; Seaman, W E (1991) Characterization of signal-transducing molecules on natural killer cells. Biochem Soc Trans 19:265-8