Barresi Vincenza, Di Bella Virginia, Lo Nigro Luca, Privitera Anna Provvidenza, Bonaccorso Paola, Scuderi Chiara, Condorelli Daniele Filippo
Department of Biomedical and Biotechnological Sciences, Section of Medical Biochemistry, University of Catania, 95123 Catania, Italy.
Cytogenetic-Cytofluorimetric-Molecular Biology Lab, 95123 Catania, Italy.
iScience. 2023 May 24;26(6):106949. doi: 10.1016/j.isci.2023.106949. eCollection 2023 Jun 16.
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.
蛋白酶临时抑制剂是真正的底物，它们以高亲和力结合催化位点，但降解缓慢，因此在特定的时间窗口内起到抑制剂的作用。丝氨酸肽酶抑制剂卡扎尔型（SPINK）家族具有这种功能特性，但其生理意义尚未得到充分探索。SPINK2在某些造血系统恶性肿瘤中的高表达促使我们研究其在成人骨髓中的作用。我们在此报告SPINK2在造血干细胞和祖细胞（HSPCs）以及动员的分化簇34（CD34）细胞中的生理表达。我们确定了SPINK2的降解常数，并推导了一个数学关系，预测围绕分泌SPINK2的HSPCs的靶蛋白酶活性受抑制区域。对SPINK2潜在靶蛋白酶的分析揭示了PRSS2和PRSS57在HSPCs中的表达。我们的综合结果表明，SPINK2及其靶丝氨酸蛋白酶可能在造血干细胞龛内的细胞间通讯中发挥作用。
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