Abstract

The objectives of our Research program are: 1) to determine the basis of the differing biology of Abelson MuLV and the HZ-abl-FeSV; 2) to identify and characterize viral oncogenes in new FeSV strains. The HZ-3590-FeSV has been recently isolated in our laboratories from a multicentric fibrosarcoma. The characterization of the oncogene of this virus revealed homology with the oncogene abl of Abelson-MuLV. Like the A-MuLV it specifies a gag-abl protein with protein kinase activity. In order to understand the differing biology we will investigate the in vivo and in vitro target specificities of this virus and evaluate the contribution of the v-abl insert and of the LTR to the biological properties of this virus. We will clone the integrated HZ-abl-FeSV genome, and we will characterize the v-abl insert. We will determine the sequence relationship between the cat-v-abl and the mouse c-abl and v-abl boundaries. We will sequence the v-abl boundaries and the LTR of this virus. We will construct LTR-gage-abl chemeras in order to investigate whether LTR sequences determine the target specificities of the virus. We will investigate the targets for transformation and consequences of transformation by the abl-FeSV and the in vitro made recombinant viruses: by inoculation into neonate mice and kittens, by in vitro transformation assays, by analyzing the phenotype of the transformants. Three feline sarcoma viruses have been characterized extensively. Two of them contain the oncogene fes, which is related to the avian oncogene fps. A third contains the oncogene fms. We have recently characterized two new FeSV's, the PI-FeSV and the HZ-3590-FeSV. In the PI-FeSV sequences related to the Simian Sarcoma Virus (SSV) oncogene sis were identified. In the HZ-3590-FeSV sequences related to the oncogene abl of Abelson MuLV. More FeSV's are being isolated in W. D. Hardy's Laboratory. We therefore will continue our effort to characterize new FeSV's

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032926-03
Application #
3170789
Study Section
Virology Study Section (VR)
Project Start
1983-05-01
Project End
1986-10-31
Budget Start
1985-05-01
Budget End
1986-10-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Vosseller, K; Stella, G; Yee, N S et al. (1997) c-kit receptor signaling through its phosphatidylinositide-3'-kinase-binding site and protein kinase C: role in mast cell enhancement of degranulation, adhesion, and membrane ruffling. Mol Biol Cell 8:909-22
Lerner, N B; Nocka, K H; Cole, S R et al. (1991) Monoclonal antibody YB5.B8 identifies the human c-kit protein product. Blood 77:1876-83
Nocka, K; Tan, J C; Chiu, E et al. (1990) Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J 9:1805-13
Tan, J C; Nocka, K; Ray, P et al. (1990) The dominant W42 spotting phenotype results from a missense mutation in the c-kit receptor kinase. Science 247:209-12
Majumder, S; Ray, P; Besmer, P (1990) Tyrosine protein kinase activity of the HZ4-feline sarcoma virus P80gag-kit-transforming protein. Oncogene Res 5:329-35
Huang, E; Nocka, K; Beier, D R et al. (1990) The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 63:225-33
Nocka, K; Buck, J; Levi, E et al. (1990) Candidate ligand for the c-kit transmembrane kinase receptor: KL, a fibroblast derived growth factor stimulates mast cells and erythroid progenitors. EMBO J 9:3287-94
Manova, K; Nocka, K; Besmer, P et al. (1990) Gonadal expression of c-kit encoded at the W locus of the mouse. Development 110:1057-69
Nocka, K; Majumder, S; Chabot, B et al. (1989) Expression of c-kit gene products in known cellular targets of W mutations in normal and W mutant mice--evidence for an impaired c-kit kinase in mutant mice. Genes Dev 3:816-26
Qiu, F H; Ray, P; Brown, K et al. (1988) Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J 7:1003-11

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