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Blood. 2016 Feb 18;127(7):927-37. doi: 10.1182/blood-2015-07-659185. Epub 2015 Nov 23.

Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation.

Author information

1
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
2
Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China; and.
3
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, China.

Abstract

The sterile-20 kinase misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1) is involved in many important cellular processes such as growth, cytoskeletal rearrangement, and motility. Here, with MINK1-deficient (MINK1(-/-)) mice, we showed that MINK1 plays an important role in hemostasis and thrombosis via the regulation of platelet functions. In the tail-bleeding assay, MINK1(-/-) mice exhibited a longer bleeding time than wild-type (WT) mice (575.2 ± 59.7 seconds vs 419.6 ± 66.9 seconds). In a model of ferric chloride-induced mesenteric arteriolar thrombosis, vessel occlusion times were twice as long in MINK1(-/-) mice as in WT mice. In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on a collagen matrix under arterial shear conditions was significantly reduced in MINK1(-/-) platelets. Moreover, MINK1(-/-) platelets demonstrated impaired aggregation and secretion in response to low doses of thrombin and collagen. Furthermore, platelet spreading on fibrinogen was largely hampered in MINK1(-/-) platelets. The functional differences of MINK1(-/-) platelets could be attributed to impaired adenosine 5'-diphosphate secretion. Signaling events associated with MINK1 appeared to involve extracellular signal-regulated kinase, p38, and Akt. Hence, MINK1 may be an important signaling molecule that mediates mitogen-activated protein kinase signaling and participates in platelet activation and thrombus formation.

PMID:
26598717
DOI:
10.1182/blood-2015-07-659185
[Indexed for MEDLINE]
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