# EPIDERMAL GROWTH FACTOR

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 1994 · $251,711

## Abstract

The overall aim of our studies has been to elucidate the biological
significance of the presence in higher organisms (including human) of both
the hormone-like polypeptide, epidermal growth factor (EGF), and receptors
for this peptide. At the molecular level we hope to understand the
biochemical steps leading from the binding of EGF by receptors on the cell
membrane to the activation of RNA and protein synthesis and to the final
induction of DNA synthesis.  Key elements in the molecular study of EGF
action have been our isolation of the receptor for EGF, the finding that
the receptor is a tyrosine-specific EGF-activated protein kinase, and the
demonstration that EGF together with its receptor/kinase are internalized
by way of endocytic vesicles.

In this proposal we plan to exploit our new finding that in the living
mouse, novel tyrosine phosphorylated substrates can be detected in all
tissues examined following the intraperitoneal administration of EGF. In
view of the large amount of tissue available, the ease of manipulation and
the physiological relevance of the in situ detected substrates, the
detailed examination of signal transduction in this system should prove
very fruitful. We have already identified SHC as an EGF dependent tyrosine
phosphorylated substrate in the mouse liver and have detected a 92 kDa
tyrosine phosphorylated protein that appears in liver nuclei within
minutes following the administration of EGF.

My specific aims are: (1) Isolate and characterize the tyrosine-
phosphorylated 92 kDa protein that we have detected in nuclei of liver
cells following the administration of EGF to adult mice and prepare
polyclonal antibodies to this protein. (2) Determine whether the same
nuclear response can be detected in other tissues of the adult mouse, as
well as the placenta and fetal tissue during development. (3) Identify
other EGF induced tyrosine phosphorylated proteins that we have detected
in various tissues of the mouse. (4) Attempt to replicate our results in
vitro, using liver slices, liver minces, primary liver cells, or liver
cell lines where labeling experiments are easily performed. (5) Attempt
cell-free reconstitution experiments to begin to understand the
biochemical mechanisms involved in signal transduction.

## Key facts

- **NIH application ID:** 2194351
- **Project number:** 2R01HD000700-31
- **Recipient organization:** VANDERBILT UNIVERSITY
- **SAM.gov UEI:** GTNBNWXJ12D5
- **Principal Investigator:** STANLEY COHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $251,711
- **Award type:** 2
- **Project period:** 1979-04-01 → 1999-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2194351

## Citation

> US National Institutes of Health, RePORTER application 2194351, EPIDERMAL GROWTH FACTOR (2R01HD000700-31). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2194351. Licensed CC0.

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