# MECHANISM OF ACTION OF A HUMAN GRANULOPOIETIN

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1991 · $215,117

## Abstract

Human granulocyte-macrophage colony-stimulating factor (GM-CSF)
stimulates the growth of myeloid progenitor cells, as well as
enhancing the functional activity of circulating neutrophils,
monocytes, and eosinophils.  Evidence in vitro and in vivo suggests
that GM-CSF is a potent granulopoietin which plays a critical role
in host defense and inflammation; clinical trials employing GM-CSF
in cancer therapy, bone marrow transplantation, and
immunodeficiency disorders, are currently in progress.  We have
previously characterized numerous biological functions of GM-CSF
on both immature progenitor cells and mature neutrophils and
eosinophils.  We have identified a low number of high affinity GM-
CSF binding sites on all responsive target cells, and characterized
the roles of Ca++, pH, and arachidonic acid release in neutrophil
priming by GM-GSF.  In this Continuation Application, we propose
to extend our studies on the GM-CSF receptor to obtain purified
preparations for biochemical characterization.  We propose to
continue studies on signal transduction processes, and to explore
the function of GTP-binding proteins, protein kinases, and
diacylglycerol in GM-CSF action.  Several strategies are proposed
to isolate cDNA clones encoding the GM-CSF receptor; we will
perform site-directed mutagenesis to identify and characterize the
ligand binding and intracellular domains of the molecule.  We will
also characterize the expression of the receptor in primary cells
and tissues, as well as experimentally addressing the results of
overexpression of native and modified receptor molecules.  In
addition to our studies on the GM-CSF receptor and its membrane
signal transduction mechanisms, we are studying specific genes
whose expression may be directly induced by GM-CSF, including early
response genes, as well as cellular oncogenes known to be expressed
in myeloid cells.  We will characterize the pattern of gene
expression in both dividing and terminally differentiated cells in
response to GM-CSF.  The ultimate goal of this work is to identify
one or more "representative" GM-CSF-responsive genes.  We will
isolate genomic clones, prepare recombinant constructs containing
the 5' promoter region and, by means of deletion analysis and site-
directed mutagenesis, identify nucleotide sequences responsive to
GM-CSF treatment.

The goal of these studies is to fully characterize the response of
both normal and neoplastic myeloid cells to the granulopoietin GM-
CSF.  The results will provide an enhanced understanding of the
physiologic role of GM-CSF in granulopoiesis; this knowledge is
essential to design rational therapeutic strategies employing GM-
CSF.

## Key facts

- **NIH application ID:** 3179759
- **Project number:** 5R01CA040163-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** JUDITH Cheryl GASSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $215,117
- **Award type:** 5
- **Project period:** 1985-07-01 → 1993-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179759

## Citation

> US National Institutes of Health, RePORTER application 3179759, MECHANISM OF ACTION OF A HUMAN GRANULOPOIETIN (5R01CA040163-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179759. Licensed CC0.

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