# EARLY CELLULAR CHANGES IN VIRAL ONCOGENESIS

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 1987 · $173,332

## Abstract

When cells become transformed by Rous sarcoma virus (RSV) they undergo
numerous biochemical and regulatory changes which collectively constitute
the "transformed phenotype."  All the manifestations of the transformed
phenotype are dependent on the continuous activity of the viral
transforming protein, pp60src, which has a tyrosine-specific protein kinase
actvity.  Genetic evidence indicates that pp60src has severa
physiologically significant cellular targets with which it interacts to
generate the transformed phenotype, and direct biochemical analysis reveals
that numerous proteins become phosphorylated on tyrosine during
transformatin by RSV.  However, it is not know which of the
tyrosine-phosphorylated proteins are physiologically significant targets
nor what role these phosphorylations play in the genesis of the transformed
phenotype.

In this application, we propose a biochemical and genetic analysis of the
intermediate steps leading from tyrosine phosphorylation by pp60src to the
transformed phenotype.  to simplify this analysis we will focus on
biochemical and regulatory events which are shared by mitogen-treated and
RSV-transformed cells:

1.  We will isolate cellular variants which are altered in their response
to pp60src or mitogenic agents.  Refractoriness to either increased growth
or increased glucose transport will be used as the basis for selection.
Such variants may carry mutations in genes coding for targets of pp60src.

2.  We will purify and characterize selected phosphotyrosine-containing
proteins, with the first priority being to purify a protein of 42,000 Mr
which is phosphorylated in both mitogen-stimulated cells and in
RSV-transformed cells.  The purified proteins will be used to raise
monoclonal antibodies  or antisera for studies on localization, for
micro-injection and for direct functional studies.

By taking the approach of biochemical genetics, we hope to define some of
the intermediate steps in transformation by RSV and particularly the role
of specific tyrosine phosphorylations in growth control and malignant
transformation.

## Key facts

- **NIH application ID:** 3177841
- **Project number:** 5R01CA039076-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **SAM.gov UEI:** JJG6HU8PA4S5
- **Principal Investigator:** MICHAEL J. WEBER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $173,332
- **Award type:** 5
- **Project period:** 1984-06-01 → 1989-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177841

## Citation

> US National Institutes of Health, RePORTER application 3177841, EARLY CELLULAR CHANGES IN VIRAL ONCOGENESIS (5R01CA039076-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177841. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*