# RECEPTORS FOR TRANSFORMING GROWTH FACTOR-BETA

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 1993 · $264,478

## Abstract

Transforming growth factor-beta (TGF-beta) is prototypic of a large family
of paracrine polypeptides that are present in organisms from insects to
humans and involved in processes ranging from embryogenic pattern formation
and morphogenesis to regulation of endocrine systems.  Their mechanism of
action is unknown.  Our appreciation of the complexity of the TGF-beta
system has escalated dramatically in the last five years.  TGF-beta exists
in multiple isoforms that regulate cell growth, differentiation, adhesion,
migration and extracellular matrix deposition.  TGF-beta is thought to play
crucial roles in organismal development and tissue repair processes.
Excess of TGF-beta activity can lead to fibrotic disorders and
immunosuppression.  Failure of TGF-beta to inhibit cell proliferation can
promote or contribute to oncogenesis.  The wealth of information that has
accumulated during recent years on the structure, distribution and activity
of the TGF-betas contrasts with the scanty understanding of its mechanism
of action.  The intracellular components known to play some role in
mediating TGF-beta action are very few.  The membrane receptors implicated
in TGF-beta signal transduction have been identified only recently, and
their mode of signaling is completely unknown.  The long-term goal of this
project is to elucidate the mechanisms that initiate and mediate TGF-beta
signal transduction.  To achieve this goal, I propose to molecularly clone
TGF-beta receptor components I and II by taking advantage of their known
properties and of a panel of cell mutants that have specific defects in
these receptor components.  The cloning of these cDNAs will allow a
structural and functional analysis of the TGF-beta receptor and should lead
to identification of the TGF-beta signaling mechanism.  It should also
assist in identifying analogous receptors for other members of the TGF-beta
superfamily.  To complement this approach, I also propose to clone cDNAs
whose products suppress cellular responsiveness to TGF-beta.  Such
antagonists or negative regulators of TGF-beta action will be important as
indicators of the nature of the signaling pathway.  Finally, I propose to
molecularly clone and functionally characterize betaglycan, and integral
membrane proteoglycan whose core protein binds TGF-beta with high affinity
and whose carbohydrate chains may bind to specific proteins in cell
membranes and extracellular matrices.  Betaglycan, which may function as a
major pericellular reservoir and/or regulator of TGF-beta presentation to
the signaling receptors, has been purified to homogeneity in our laboratory
to characterize its function and as a step towards cloning its cDNA.
Future progress towards the aims set forth in this proposal should clarify
important gaps in our current understanding of fundamental mechanisms that
control animal cell growth and phenotype.

## Key facts

- **NIH application ID:** 3172348
- **Project number:** 5R01CA034610-11
- **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:** 1993
- **Award amount:** $264,478
- **Award type:** 5
- **Project period:** 1983-05-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172348

## Citation

> US National Institutes of Health, RePORTER application 3172348, RECEPTORS FOR TRANSFORMING GROWTH FACTOR-BETA (5R01CA034610-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3172348. Licensed CC0.

---

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