# Proteinase systems in insect hemolymph

> **NIH NIH R37** · KANSAS STATE UNIVERSITY · 2020 · $375,000

## Abstract

Some insect immune responses require activation of plasma proteins by proteases in hemolymph. These
include proteolytic processing of cytokine precursors, including the Toll ligand Spatzle and the plasmatocyte
spreading peptide. Another protease-mediated response is the activation of phenoloxidase zymogens,
which then oxidize circulating diphenols to quinones, precursors for deposition of melanin on the surface of
invading organisms. Such innate immune responses are likely to affect the outcome of infections of insect
vectors with the pathogens and parasites they transmit. Responses modulated by proteases in blood are not
simply linear pathways, but instead each protease may cleave multiple substrates, and active proteases
may be regulated by several inhibitors. Previous work from our laboratory and others has established the
lepidopteran insect, Manduca sexta, as a model system well suited for biochemical investigation of
hemolymph proteases. The new availability of a M. sexta genome sequence make possible the investigation
of serine protease webs in M. sexta hemolymph, using biochemical systems approaches. This research will
be aimed at understanding hemolymph protease pathways and their regulation. The proteomics approach
may reveal previously undiscovered protease-activated immune molecules of insects. The specific aims of
the project are to:
1. Characterization of the plasma protein degradome to identify substrates for clip domain proteases and
study their immune functions.
2. Continue to study the regulation of protease pathways in hemolymph by serpins.
3. Investigate the activation of the pathway-initiating modular protease, HP14.
The long term goals of the research are to gain a thorough understanding of the regulation of protease
cascades that mediate innate immune responses in Manduca, to apply this knowledge to insect vectors of
human diseases, and to apply advantages of the Manduca system for fundamental studies on the regulation
of serine protease activity.

## Key facts

- **NIH application ID:** 9893918
- **Project number:** 5R37GM041247-31
- **Recipient organization:** KANSAS STATE UNIVERSITY
- **Principal Investigator:** Michael R Kanost
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $375,000
- **Award type:** 5
- **Project period:** 1991-07-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893918

## Citation

> US National Institutes of Health, RePORTER application 9893918, Proteinase systems in insect hemolymph (5R37GM041247-31). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9893918. Licensed CC0.

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