# LIGAND-RECEPTOR-G PROTEIN DYNAMICS & NEUTROPHIL RESPONSE

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO · 1992 · $172,074

## Abstract

The activation of many cell types involves a multistep pathway
initiated by the binding of ligand (L) to cell surface receptors (R)
and followed by a transmembrane interaction of LR with guanine
nucleotide binding proteins (G).  The neutrophil, whose G is a
novel protein which activates phospholipase C, is an ideal model
system in which to study LRG dynamics.  Neutrophils, the most
numerous of the human white blood cells, play a pivotal role in
host defense and contribute to tissue injury which accompanies
inflammation.  Fluorescent ligands (both agonists and antagonists)
for several receptors have already been prepared.  The ligands
together with homogeneous, real-time, fluorescent methods make
possible for the first time a detailed analysis of LRG dynamics
and its role in cell activation.  The formyl peptide receptor of the
neutrophil has already been identified in three states:  1) a
ternary LRG complex which is slowly dissociating for L and
sensitive to the presence of guanine nucleotide; 2) a rapidly
dissociating LR complex; and 3) a distinct, slowly dissociating
state insensitive to guanine nucleotide which is hypothesized to
arise subsequent to cell activation.  During cell activation there
appears to be interconversion among these forms, with the first
and perhaps the second active in transduction.  These states have
unique biochemical characteristics and can be studied
individually.  In order to understand 1) the roles of these  states,
2) the dynamics of their interconversion, and 3) their interactions
with G proteins during cell activation, we will first define the
conditions of formation, stabilization and interconversion among
the states in cell and membrane preparations, and where possible,
with pure proteins.  Then we will define the rate processes and
thermodynamics associated with the states and their
interconversions.  We will use pulse stimulation and rapid kinetic
techniques to assess the appearance and disapperance of the
states during cell activation.  We will use mathematical modelling
to gain mechanistic insight into the transduction pathway.  By
comparing results for different agonists we expect to gain
fundamental insight into the basis of agonist efficacy.  By
comparing the agonists and antagonists we expect to define
fundamental differences in the ability of agonists or antagonists
to interact with or promote interconversion among receptor
states.  By contrasting results obtained with formyl peptides and
fluorescent C5a we expect to gain insight into the uniqueness or
generality of LRG dynamics at receptors for distinct ligands.

## Key facts

- **NIH application ID:** 3128455
- **Project number:** 5R01AI019032-11
- **Recipient organization:** UNIVERSITY OF NEW MEXICO
- **SAM.gov UEI:** F6XLTRUQJEN4
- **Principal Investigator:** LARRY A. SKLAR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $172,074
- **Award type:** 5
- **Project period:** 1990-07-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128455

## Citation

> US National Institutes of Health, RePORTER application 3128455, LIGAND-RECEPTOR-G PROTEIN DYNAMICS & NEUTROPHIL RESPONSE (5R01AI019032-11). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128455. Licensed CC0.

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