Abstract

Our objective is to understand the role of polyoma T antigens in cell transformation. The middle-size (mT) antigen is associated with two cellular proteins, p60c-src (the cellular homologue of the Rous sarcoma virus transforming protein) and a 61K protein, both of which are implicated in transformation. We will study the nature and function of the association, using modified mT proteins with altered structure and transforming abilities. We will study the modification and enhancement of p60c-src activity as a result of its association with the mT antigen. We will test whether altered mT proteins are able to complement for transformation, using viruses or cloned DNA's encoding mT proteins with altered transforming abilities. We will use retroviral vectors to introduce individual T antigens into cells with high efficiency, and will study the interaction of the cells with purified growth factors to clarify the effects of the T antigens on control of the cell cycle. Some human neuroblastoma cell lines contain p60c-src with enhanced protein kinase activity and N-terminal tyrosine phosphorylation, resembling the p60C-src associated with the mT antigen in polyoma-transformed cells. We will study whether cellular proteins in some tumor cells can form complexes with p60c-src and modify its activity, perhaps contributing to cell transformation and malignancy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA013884-15
Application #
3481678
Study Section
Virology Study Section (VR)
Project Start
1975-09-01
Project End
1991-02-28
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
15
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Yanochko, Gina M; Eckhart, Walter (2006) Type I insulin-like growth factor receptor over-expression induces proliferation and anti-apoptotic signaling in a three-dimensional culture model of breast epithelial cells. Breast Cancer Res 8:R18
Arbet-Engels, C; Tartare-Deckert, S; Eckhart, W (1999) C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. J Biol Chem 274:5422-8
Arbet-Engels, C; Janknecht, R; Eckhart, W (1999) Role of focal adhesion kinase in MAP kinase activation by insulin-like growth factor-I or insulin. FEBS Lett 454:252-6
Kanemitsu, M Y; Jiang, W; Eckhart, W (1998) Cdc2-mediated phosphorylation of the gap junction protein, connexin43, during mitosis. Cell Growth Differ 9:13-21
Kanemitsu, M Y; Loo, L W; Simon, S et al. (1997) Tyrosine phosphorylation of connexin 43 by v-Src is mediated by SH2 and SH3 domain interactions. J Biol Chem 272:22824-31
Warn-Cramer, B J; Lampe, P D; Kurata, W E et al. (1996) Characterization of the mitogen-activated protein kinase phosphorylation sites on the connexin-43 gap junction protein. J Biol Chem 271:3779-86
Lau, A F; Kurata, W E; Kanemitsu, M Y et al. (1996) Regulation of connexin43 function by activated tyrosine protein kinases. J Bioenerg Biomembr 28:359-68
Glenn, G M; Eckhart, W (1995) Amino-terminal regions of polyomavirus middle T antigen are required for interactions with protein phosphatase 2A. J Virol 69:3729-36
Rigaudy, P; Simon, S; Hunter, T et al. (1994) Antibodies specific for the neuronal form of the Src protein elicited by an antigenized antibody. DNA Cell Biol 13:585-91
Srinivas, S; Schonthal, A; Eckhart, W (1994) Polyomavirus middle-sized tumor antigen modulates c-Jun phosphorylation and transcriptional activity. Proc Natl Acad Sci U S A 91:10064-8

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