Abstract

The basic objective of this research is the elucidation of the mechanism of neoplastic transformation of cells. Special emphasis will be placed on the biochemical analysis of the process of transformation in cells infected with avian sarcoma viruses. The studies will include the determination of subcellular localization of oncogene products, and identification of target host protein(s) whose phosphorylation is critical for cell transformation, and the characterization of changes in the expression of normal cellular genes in the process of transformation. Efforts will be made to identify cellular genes required for transformation. Analysis of the structure and functions of cellular and viral oncogene products and the conditions required for the conversion of the former to the latter will be investigated. As a part of this project we will analyze the mechanism of activation of the c-src protein by polyoma virus. The basis for tissue specific transformation by some oncogenic viruses will be explored. In order to understand the possible function of certain proto- oncogenes in normal cells, their expression will be analyzed in various cells at different developmental stages of animals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA044356-03
Application #
3479562
Study Section
(SRC)
Project Start
1987-07-01
Project End
1994-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Kirsch, Kathrin; Kensinger, Margaret; Hanafusa, Hidesaburo et al. (2002) A p130Cas tyrosine phosphorylated substrate domain decoy disrupts v-crk signaling. BMC Cell Biol 3:18
Kirsch, K H; Georgescu, M M; Shishido, T et al. (2001) The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src homology 3 domain interaction. J Biol Chem 276:4957-63
Shishido, T; Akagi, T; Chalmers, A et al. (2001) Crk family adaptor proteins trans-activate c-Abl kinase. Genes Cells 6:431-40
Shishido, T; Akagi, T; Ouchi, T et al. (2000) The kinase-deficient Src acts as a suppressor of the Abl kinase for Cbl phosphorylation. Proc Natl Acad Sci U S A 97:6439-44
Akagi, T; Shishido, T; Murata, K et al. (2000) v-Crk activates the phosphoinositide 3-kinase/AKT pathway in transformation. Proc Natl Acad Sci U S A 97:7290-5
Wong, B R; Besser, D; Kim, N et al. (1999) TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src. Mol Cell 4:1041-9
Georgescu, M M; Kirsch, K H; Shishido, T et al. (1999) Biological effects of c-Mer receptor tyrosine kinase in hematopoietic cells depend on the Grb2 binding site in the receptor and activation of NF-kappaB. Mol Cell Biol 19:1171-81
Besser, D; Bromberg, J F; Darnell Jr, J E et al. (1999) A single amino acid substitution in the v-Eyk intracellular domain results in activation of Stat3 and enhances cellular transformation. Mol Cell Biol 19:1401-9
Kirsch, K H; Georgescu, M M; Ishimaru, S et al. (1999) CMS: an adapter molecule involved in cytoskeletal rearrangements. Proc Natl Acad Sci U S A 96:6211-6
Georgescu, M M; Kirsch, K H; Akagi, T et al. (1999) The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci U S A 96:10182-7

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