Researchers have identified serine threonine kinase 10 as a key regulator of platelet function, haemostasis and thromboinflammation, providing new insight into mechanisms that drive thrombosis and inflammatory vascular disease.
Expression And Functional Role
Serine threonine kinase 10 is a member of the Ste20 family of kinases and is known to regulate lymphocyte adhesion. Using quantitative phosphoproteomic analysis, investigators observed increased phosphorylation of this kinase in activated platelets, prompting further investigation into its functional role.
The team first confirmed expression of the kinase in both human and mouse platelets. They then generated megakaryocyte and platelet specific knockout mice to assess its contribution to platelet biology. Loss of platelet kinase expression led to impaired haemostasis and reduced arterial thrombosis in vivo, demonstrating a critical role in thrombus formation.
Consistent with these findings, multiple platelet functions were significantly reduced following gene deletion. These included platelet aggregation, alpha granule release, activation of integrin alpha IIb beta 3, procoagulant activity, platelet spreading and clot retraction. Together, the results indicate broad impairment of platelet activation pathways.
Molecular Mechanism Identified
Quantitative phosphoproteomic profiling revealed several dysregulated phosphoproteins in knockout platelets, with enrichment in pathways related to platelet activation and focal adhesion. Using immunoprecipitation combined with mass spectrometry and phosphorylation screening, the researchers identified integrin linked protein kinase as a key interacting partner.
Further analysis showed that deletion of serine threonine kinase 10 significantly reduced phosphorylation of integrin linked protein kinase at serine 343. In vitro phosphorylation assays confirmed that the kinase directly phosphorylates integrin linked protein kinase at this site. Inhibition of calcium signalling, protein kinase C or phosphatidylinositol 3 kinase also suppressed phosphorylation of the kinase in activated platelets, placing it within established platelet signalling networks.
Impact On Thromboinflammation
Beyond haemostasis, deletion of platelet serine threonine kinase 10 reduced platelet neutrophil interactions, neutrophil accumulation and neutrophil extracellular trap formation. These changes were associated with reduced thromboinflammation and improved survival in mouse models of sepsis.
Importantly, increased activation of both the kinase and integrin linked protein kinase was observed in platelets from septic mice and from patients with sepsis, supporting clinical relevance.
The authors conclude that serine threonine kinase 10 plays a previously unrecognised role in regulating platelet function, arterial thrombosis and thromboinflammation. They suggest it may represent a promising therapeutic target for thrombotic and cardiovascular diseases, as well as inflammatory conditions such as sepsis.
Reference
Li Y et al. STK10 regulates platelet function in arterial thrombosis and thromboinflammation. Blood. 2026;147(1):73-86.
