# RECEPTORS & TARGETS FOR TRANSFORMING GROWTH FACTOR BETA

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1989 · $303,654

## Abstract

It is proposed to define molecular events involved in cellular activation
by type Beta transforming growth factor (TGfBeta).  TGFBeta is a hormonally
active polypeptide protein in blood platelets and in other normal and
transformed sources.  The cellular actions of TGFBeta include induction of
the transformed phenotype in mesenchimal cells, inhibition of proliferation
in epithelial and carcinoma cells, and control of differentiation of other
cell types.  We have identified high-affinity cellular receptors for
TGFBeta and accumulated information on the functional and structural
properties of this receptor type.  However, the molecular basis for the
cellular actions of TGFBeta is unknown.  We are addressing this problem in
two complementary ways.  First, we propose to purify this receptor molecule
from sources that provide working amounts of it, using specific
affinity-chromatography steps.  Purified receptor preparations will be used
to validate the disulfide-linked subunit structure that we have proposed
for the TGFBeta receptor based on receptor affinity-labeling studies.  The
structural and ligand binding properties of the purified receptor will be
characterized in detail.  We will seek to raise monoclonal antibodies
against the TGFBeta receptor.  Antibodies will be used to further
characterize the structure and biochemistry of TGFBeta receptors.

The second way in which we are studying TGFBeta action is by identifying
molecular events induced by TGFBeta and potentially involved in its varied
cellular actions.  We are examining the extracellular matrix (EM) as a
potentially key target for TGFBeta because, i) alterations of the EM can
modulate the proliferation and differentiation of many cell types, ii) the
EM is critically involved in the process of wound healing, a process which
platelet TGFBeta is physiologically targeted for, and iii) we find that
TGFBeta activates sharply the production and incorporation of fibronectin,
a central component of the EM.  We propose to examine in detail the TGFBeta
receptor-mediated stimulation of fibronectin synthesis in fibroblasts and
other cell types at the protein and mRNA levels.  It is expected that the
double approach at the receptor/postreceptor levels that we propose will
generate information critical for understanding the key molecular events
involved in TGFBeta action.

## Key facts

- **NIH application ID:** 3172349
- **Project number:** 7R01CA034610-07
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **SAM.gov UEI:** KUKXRCZ6NZC2
- **Principal Investigator:** JOAN MASSAGUE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $303,654
- **Award type:** 7
- **Project period:** 1983-05-01 → 1991-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172349

## Citation

> US National Institutes of Health, RePORTER application 3172349, RECEPTORS & TARGETS FOR TRANSFORMING GROWTH FACTOR BETA (7R01CA034610-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172349. Licensed CC0.

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