# REGULATION OF PROTEASE NEXIN 1 ACTIVITY AND SECRETION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 1992 · $190,941

## Abstract

Our goal is to elucidate mechanisms by which regulatory serine proteases
are controlled at and near the cell surface by three protease nexins (PN-1,
PN-2 and PN-3) which we identified in earlier studies.  The PNs are protein
protease inhibitors that are synthesized and released by a variety of
cultured cells.  They form covalent complexes with certain proteases in the
extracellular environment; the complexes bind back to the cells and are
rapidly internalized and degraded.  With purified PN-1 and seven regulatory
proteases it inactivates, we will measure second order association rate
constants to provide a quantitative foundation for our studies.  Then,
based on our finding that the surface of fixed fibroblasts accelerates the
reaction between PN-1 and thrombin, we will determine if the reactions
between PN-1 and the other proteases are similarly accelerated.  Some of
the acceleration of the reaction between PN-1 and thrombin appears to
involve cell surface/extracellular matrix glycosaminoglycans.  We will
check this by treating fibroblasts with glycosaminoglycan lyases, fixing
the cells, and examining the effect of this on the ability of the cells to
accelerate the reactions.  In complimentary studies we will examine the
effects of purified glycosaminoglycans, in the absence of cells, on the
reactions between PN-1 and the proteases.  About 50% of the acceleration of
the PN-1 and thrombin reactions appears to involve the Mr=150,000 cell
surface binding sites for thrombin.  We will study the basis of this and
determine if there are cell surface binding sites for the six other
regulatory proteases that might similarly participate in their control.
With PN-2 that we recently purified to homogeneity, we will screen for
serine proteases it effectively inactivates, measure second order
association rate constants with them, and begin studies on PN-2 along the
lines of the above studies for PN-1.  Finally, we will purify PN-3 from
serum-free culture medium conditioned by fibroblasts.

## Key facts

- **NIH application ID:** 3122503
- **Project number:** 5R01AG010598-10
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **SAM.gov UEI:** MJC5FCYQTPE6
- **Principal Investigator:** DENNIS D CUNNINGHAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $190,941
- **Award type:** 5
- **Project period:** 1991-09-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122503

## Citation

> US National Institutes of Health, RePORTER application 3122503, REGULATION OF PROTEASE NEXIN 1 ACTIVITY AND SECRETION (5R01AG010598-10). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3122503. Licensed CC0.

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