# ROLE OF C-SRC IN RETROVIRAL TRANSFORMATION

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1991 · $160,358

## Abstract

Oncogene-mediated transformation results in the disruption of
normal cellular growth-control.  Understanding the role normal
counterparts of transforming agents play in cellular homeostasis
will enhance our ability to decipher the molecular mechanisms by
which oncogenic agents cause this system to go awry.  Our studies
have provided two lines of evidence which suggest that the proto-
oncogene product, pp60c-src, is involved in the mitogenic
response of cells to epidermal growth factor (EGF).  First, murine
C3H10T1/2 fibroblasts constitutively overexpressing pp60c-src
exhibit a hyper-responsiveness to EGF (as measured by 3H-
thymidine incorporation) when compared to the response of
stimulated, parent cells.  Second, a dramatic negative regulation
of pp60c-src specific kinase activity occurs in quail embryo
fibroblasts transformed by the avian erythroblastosis virus (AEV),
which encodes aberrant forms of the thyroxin receptor (v-erb A)
and the EGF receptor (v-erb B).  The experiments outlines in this
proposal have two inter-related aims.  The first is to determine
the molecular mechanism for the enhanced responsiveness of c-
src overexpressors to EGF by analyzing and comparing levels of
second messengers, critical protein kinases and expression of
proto-oncogenes in mitogen-stimulated parent and overexpressor
lines.  Analysis of cells overexpressing c-src bearing site-directed
mutations in the molecule and microinjection of monoclonal
antibodies with specificities to defined epitopes will be carried
out to determine regions within the c-src protein which are
required for the interaction with cellular components that result
in the enhanced response to growth factors.  The second aim is to
determine the mechanism of down-modulation of pp60c-src
activity in AEV infected cells.  A genetic approach utilizing
deletion and temperature-sensitive mutants of AEV will allow us
to determine whether v-erb A or v-erb B or both are required for
this effect.  Intracellular localization studies, analysis of signal
transduction components, and purification and identification of
cellular agents which mediate the regulatory effects on pp60c-src
in uninfected and wild type and mutant infected AEV cells are
also proposed.  Together these studies have as their common goal
the elucidation of the temporal and spatial relationships of pp60c-
src to substrate and regulatory components of the EGF-dependent
signal transduction pathway(s).

## Key facts

- **NIH application ID:** 3178413
- **Project number:** 5R01CA039438-07
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** SARAH J PARSONS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $160,358
- **Award type:** 5
- **Project period:** 1985-04-01 → 1993-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178413

## Citation

> US National Institutes of Health, RePORTER application 3178413, ROLE OF C-SRC IN RETROVIRAL TRANSFORMATION (5R01CA039438-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3178413. Licensed CC0.

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