title: Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation.
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.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Dongjiao
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Pu
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Mengjiao
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Qian
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China;
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China; and.
authors.forename: Linrong
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, China; Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Hu
mesh_terms: D000244:Adenosine Diphosphate / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology* / Q000473:pathology; D002712:Chlorides / Q000633:toxicity; D005290:Ferric Compounds / Q000633:toxicity; D020935:MAP Kinase Signaling System; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013927:Thrombosis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D000244:Adenosine Diphosphate; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C024555:ferric chloride