# HUMAN CELL SURFACE ANTIGENS--TRANSFERRIN RECEPTORS

> **NIH NIH R01** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 1992 · $245,871

## Abstract

The long-term goal of this project is to understand the structure-function
relationship of the transferrin receptor and its role in cell growth.  The
proposed work will contribute to our appreciation of the molecular basis of
receptor-mediated endocytosis and recycling.  It will also contribute to
the evaluation of the transferrin receptor as a potential target for
immunotherapy in the treatment of cancer and the development of more
effective methods of antibody-mediated cell-specific drug targeting.  The
specific aims are: 1) to characterize the external domain of the human
transferrin receptor immunochemically and map the transferrin binding site
by structural analysis of chick-human hybrid receptors; 2) to determine
whether the YXRF internalization signal found in the amino-terminal
cytoplasmic domain of the human transferrin receptor is sufficient to
induce rapid endocytosis of other Type II membrane proteins; 3) to express
and isolate sufficient soluble human transferrin receptor external and
cytoplasmic domains for biophysical characterization; 4) to characterize
the interaction of the transferrin receptor cytoplasmic domain with
structural components of coated pits; 5) to investigate the role of the
human transferrin receptor cytoplasmic domain in endosome-endosome fusions;
and 6) to characterize the intracellular compartments through which the
transferrin receptor traffics during endocytosis and recycling.

To achieve these goals, we will use a broad range of experimental methods
derived from molecular biology, protein biochemistry, cell biology, and
immunology.  Specifically, we will exploit: 1) the availability of cDNAs
for the human mouse and chicken transferrin receptors; 2) a retroviral
expression system for expressing mutant human transferrin receptors in
chick embryo fibroblasts and analysis of their biological activity; 3)
high-yield protein expression systems in bacteria.  Chinese hamster ovary
cells and vaculovirus-infected insect cells that have allowed the
expression of the intact transferrin receptor, and independently, the
cytoplasmic and external domains as soluble recombinant proteins; 4) and
more than 30 monoclonal antibodies against both the external and
cytoplasmic domains of the human transferrin receptor.  A major new aspect
of the work is to develop the materials and methods necessary to determine
the 3-dimensional structure of both the cytoplasmic and external domains of
the human transferrin receptor.  The former studies will test the validity
of the model we have recently proposed that a Type I turn is the structural
recognition motif for high-efficiency endocytosis.

## Key facts

- **NIH application ID:** 3172611
- **Project number:** 5R01CA034787-10
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **SAM.gov UEI:** NNJ6BMBTFGN5
- **Principal Investigator:** IAN S TROWBRIDGE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $245,871
- **Award type:** 5
- **Project period:** 1983-06-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172611

## Citation

> US National Institutes of Health, RePORTER application 3172611, HUMAN CELL SURFACE ANTIGENS--TRANSFERRIN RECEPTORS (5R01CA034787-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172611. Licensed CC0.

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