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Titolo:
Thrombomodulin with the Asp468Tyr mutation is expressed on the cell surface with normal cofactor activity for protein C activation
Autore:
Nakazawa, F; Koyama, T; Saito, T; Shibakura, M; Yoshinaga, H; Chung, DH; Kamiyama, R; Hirosawa, S;
Indirizzi:
Tokyo Med & Dent Univ, Fac Med, Dept Internal Med 1, Bunkyo Ku, Tokyo 1138519, Japan Tokyo Med & Dent Univ Tokyo Japan 1138519 unkyo Ku, Tokyo 1138519, Japan Tokyo Med & Dent Univ, Fac Med, Sch Allied Hlth Sci, Bunkyo Ku, Tokyo 1138519, Japan Tokyo Med & Dent Univ Tokyo Japan 1138519 unkyo Ku, Tokyo 1138519, Japan
Titolo Testata:
BRITISH JOURNAL OF HAEMATOLOGY
fascicolo: 2, volume: 106, anno: 1999,
pagine: 416 - 420
SICI:
0007-1048(199908)106:2<416:TWTAMI>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
COAGULATION INHIBITORS SUBCOMMITTEE; THROMBIN-CATALYZED ACTIVATION; MYOCARDIAL-INFARCTION; STANDARDIZATION COMMITTEE; THROMBOEMBOLIC-DISEASE; ENDOTHELIAL-CELLS; LEUKEMIA-CELLS; HUMAN-PLASMA; GENE; DEFICIENCY;
Keywords:
thrombomodulin; protein C; cofactor activity for protein C activation; point mutation; thrombosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Hirosawa, S Tokyo Med & Dent Univ, Fac Med, Dept Internal Med 1, Bunkyo Ku, 5-45 Yushima 1 Chome, Tokyo 1138519, Japan Tokyo Med & Dent Univ 5-45 Yushima 1 Chome Tokyo Japan 1138519
Citazione:
F. Nakazawa et al., "Thrombomodulin with the Asp468Tyr mutation is expressed on the cell surface with normal cofactor activity for protein C activation", BR J HAEM, 106(2), 1999, pp. 416-420

Abstract

Thrombomodulin (TM) is an endothelial cell glycoprotein that acts as an anticoagulant. Mutation in the TM gene is a potential risk factor for thrombosis. The first TM mutation identified tvas a heterozygous substitution of Tfor G at nucleotide position 1456, which predicted Asp468 with Tyr in a Ser/Thr-rich domain. To evaluate the reported TM gene mutation as a possible cause of thrombosis, rye transiently tranfected a vector for TM gene carrying the mutation to mammalian COS7 cells. TM antigen levels in lysates of cells transfected with variant TM were comparable to those in preparations of normal TM. The TM cofactor activity forprotein C (PC) activation on the variant TM-expressing cells was similar to that of the control. The Michaelis constant K-m and V-max of variant TM for PC activation were shown to be similar compared to those of normal TM. The affinity of each TM for thrombin in PC activation was also similar. We obtained several stable cell lines expressing normal and variant TM. Lysate of the cell lines with normal and variant TM genes had a similar expressionlevel of TM antigen, Pulse-chase analysis showed that normal and variant TM were glycosylated and resistant to endoglycosidase Ii, indicating that the variant TM was expressed on the cell surface In a mature form. Variant TM protein is apparently expressed on the cell surface with normalcofactor activity for PC activation. It is unlikely that the TM variant directly causes thrombosis by mechanism of reduced expression or impaired cofactor activity for PC activation, which comprises a major anticoagulant activity of TM.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 08:42:32