Temporary Serine Protease Inhibition and the Role of SPINK2 in Human Bone Marrow

Overview

Journal iScience

Publisher Cell Press

Date 2023 Jun 28

PMID 37378330

Authors

Vincenza Barresi

Virginia Di Bella

Luca Lo Nigro

Anna Provvidenza Privitera

Paola Bonaccorso

Chiara Scuderi

Daniele Filippo Condorelli

Affiliations

Soon will be listed here.

Abstract

Protease temporary inhibitors are true substrates that bind the catalytic site with high affinity but are slowly degraded, thus acting as inhibitor for a defined time window. Serine peptidase inhibitor Kazal type (SPINK) family is endowed with such functional property whose physiological meaning is poorly explored. High expression of SPINK2 in some hematopoietic malignancies prompted us to investigate its role in adult human bone marrow. We report here the physiological expression of SPINK2 in hematopoietic stem and progenitor cells (HSPCs) and mobilized cluster differentiation 34 (CD34) cells. We determined the SPINK2 degradation constant and derived a mathematical relationship predicting the zone of inhibited target protease activity surrounding the SPINK2-secreting HSPCs. Analysis of putative target proteases for SPINK2 revealed the expression of PRSS2 and PRSS57 in HSPCs. Our combined results suggest that SPINK2 and its target serine proteases might play a role in the intercellular communication within the hematopoietic stem cell niche.

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