Four missense mutations identified in the protein S gene of thrombosis patients with protein S deficiency: effects on secretion and anticoagulant activity of protein S

Thrombosis Research
Hiroko TsudaNaotaka Hamasaki

Abstract

Four missense mutations, G54R, T589I, K155E, and Y595C, were identified in the protein S (PS) gene of the patients with PS deficiency and venous thrombosis. Three patients were heterozygous for the novel mutations, G54R, T589I, and Y595C, while a remaining one patient was homozygous for the K155E mutation, which is known to be a polymorphism in the Japanese population. A family study revealed that the Y595C mutation was associated with a Type I PS deficiency and the K155E mutation with a Type II PS deficiency, while no family study was performed for the patients with the G54R and T589I mutations. To determine whether these four mutations play a causative role in PS deficiency, the four PS mutants and wild-type PS were stably expressed in human embryo kidney (HEK) 293 cells. Pulse-chase experiments showed intracellular degradation and decreased secretion of the Y595C mutant. In the activated protein C (APC) cofactor assays, the specific activity of the K155E mutant decreased to 58% of that of wild-type PS. The APC cofactor activity of the three mutants, G54R, K155E, and T589I, were inhibited by C4b-binding protein (C4BP) with a dose dependency similar to that of wild-type PS. These results indicate that the Y595C and the K155E m...Continue Reading

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Citations

Oct 15, 2009·International Journal of Hematology·Jun YamanouchiMasaki Yasukawa
Sep 12, 2006·Journal of Thrombosis and Haemostasis : JTH·H OkadaT Kojima
Jun 28, 2005·Clinical Biochemistry·Sachiko KinoshitaNaotaka Hamasaki
Jun 2, 2017·The British Journal of Dermatology·R ToraiT Shimizu
Aug 16, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Cécile V DenisPeter J Lenting
Jan 10, 2013·Annals of Laboratory Medicine·Naotaka HamasakiHiroko Tsuda
Jul 30, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Misuk JiWon-Ki Min
Dec 14, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Tomohide TsudaNaotaka Hamasaki
Aug 22, 2012·Journal of Thrombosis and Haemostasis : JTH·N Hamasaki
Oct 24, 2018·Research and Practice in Thrombosis and Haemostasis·Keiko MaruyamaKoichi Kokame
Feb 26, 2010·Thrombosis Research·Makoto IkejiriMasaki Itoh

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