Naturally occurring chicken erythroblastosis is induced by non-acute retroviruses through proviral insertion-activation of the c-erbB protooncogene, which encodes epidermal growth factor receptor. The resulting oncogenic erbB molecule is a truncated receptor with deregulated tyrosine kinase activity. This system has provided a fascinating model for studying not only the mechanisms of retroviral insertional mutagenesis and retroviral transductivity but also the growth signaling by a receptor-oncogene. Substantial progress has been made in the past granting period to understand the basis of these issues. One of the striking findings is related to the tissue-specific transformation by the truncated erbB/EGFR molecule. Modulation of the structure of the receptor either in the regulatory or catalytic domain by various mutations changes the oncogenic spectrum of the viruses. The findings suggest the existence of tissue-specific interactions between the receptor and the cellular machinery. Using retrovirus as a genetic tool and other molecular biological approaches, we wish to exploit the uniqueness of the chicken c-erbB system to understand (1) the tissue-specific transformation and intracellular signaling by c-erbB and (2) the ligand-receptor interaction and extracellular signaling by c-erbB.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37CA039207-10
Application #
2089753
Study Section
Virology Study Section (VR)
Project Start
1991-01-01
Project End
1995-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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