Temporary serine protease inhibition and the role of SPINK2 in human bone marrow

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...

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Veröffentlicht in:iScience 2023-06, Vol.26 (6), p.106949-106949, Article 106949
Hauptverfasser: Barresi, Vincenza, Di Bella, Virginia, Lo Nigro, Luca, Privitera, Anna Provvidenza, Bonaccorso, Paola, Scuderi, Chiara, Condorelli, Daniele Filippo
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •Physiological SPINK2 expression in adult bone marrow and in mobilized CD34+ cells•SPINK2 expression in haematological cancers•Kinetic properties of trypsin inhibition by SPINK2•Physiological meaning of the temporary enzyme inhibition properties of SPINK2 Biochemistry; Molecular physiology; Biophysics
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2023.106949