# REGULATION OF C-REACTIVE PROTEIN EXPORT FROM THE ER

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 1992 · $101,590

## Abstract

Studies from our laboratory have shown that the half-time for secretion
of the acute phase protein, C-reactive protein (CRP), by rabbit
hepatocytes decreases dramatically in conjunction with its increased
synthesis during the acute phase response and that this is due to
downregulation of a specific high affinity binding site for CRP which
ordinarily retains this protein within the ER of normal hepatocytes.
More recently, we have identified and purified two 60 kD proteins (or two
different modified forms of the same protein) with different net charges,
designated gp6Oa and gp6Ob, which fulfil the necessary criteria for the
previously observed high and low affinity binding site for CRP.  The
overall goal of this proposal is to elucidate the mechanisms which
regulate the activity of the CRP binding site during the acute phase
response and to directly investigate its role in the regulation of CRP
secretion.  Specific aims include 1) Characterization of the specificity
and affinity of CRP's binding to gp6O's employing biotinated CRP and
immobilized gp6O in an ELISA. 2) Peptide mapping and microsequencing will
be used to determine whether the two forms represent a single protein and
polyclonal antibodies will be raised in guinea pigs. 3) Synthesis,
stability, and potential modification of gp6O will be determined in
primary hepatocyte cultures incubated with either labeled methionine,
phosphorus, myristate, or sulfate employing immunoprecipitation and
SDS-PAGE. 4) Subcellular localization of gp6O's will be investigated in
saponin-permeabilized hepatocytes treated with anti-gp6O followed by
biotinated goat anti-guinea pig Ig antibody. 5) cDNA clones for gp6O will
be isolated using degenerate oligonucleotide primers in a PCR
amplification of an available rabbit cDNA library. cDNA transfection
studies will allow for direct investigation of gp6O, or its modification,
in the retention of CRP within the ER.  The serum concentration of CRP is
markedly elevated in a number if inflammatory diseases and CRP itself
appears to play a role in the modulation of the inflammatory response.
Investigation of mechanisms which control CRP secretion will contribute
to our understanding of the host response to a wide variety of
inflammatory conditions, including many of the rheumatic diseases.

## Key facts

- **NIH application ID:** 3156790
- **Project number:** 2R01AR034313-08
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **SAM.gov UEI:** HJMKEF7EJW69
- **Principal Investigator:** STEPHEN S MACINTYRE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $101,590
- **Award type:** 2
- **Project period:** 1984-07-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156790

## Citation

> US National Institutes of Health, RePORTER application 3156790, REGULATION OF C-REACTIVE PROTEIN EXPORT FROM THE ER (2R01AR034313-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156790. Licensed CC0.

---

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