A5070589320- Platelet Disorders and Treatments
- Complement system in diseases
- Blood groups and transfusion
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hemophilia Treatment and Research
- Venomous Animal Envenomation and Studies
- Signaling Pathways in Disease
- Erythrocyte Function and Pathophysiology
- Blood disorders and treatments
- Venous Thromboembolism Diagnosis and Management
- Cancer-related gene regulation
- Blood properties and coagulation
- Trypanosoma species research and implications
- Invertebrate Immune Response Mechanisms
- Protease and Inhibitor Mechanisms
- Immunodeficiency and Autoimmune Disorders
- Renal Diseases and Glomerulopathies
Washington University in St. Louis
2010-2019
Howard Hughes Medical Institute
1989-2004
Barnes-Jewish Hospital
1998
Jewish Hospital
1995
von Willebrand factor is a large multimeric plasma protein composed of identical subunits which contain four types repeated domains. essential for normal hemostasis, and deficiency the most common inherited bleeding disorder man. Four human genomic DNA cosmid libraries one bacteriophage λ library were screened with cDNA probes. Twenty positive overlapping clones characterized that span entire gene. A high-resolution restriction map was constructed ~ 75% locus total 33.8 kilobases sequenced...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHuman von Willebrand factor gene and pseudogene: structural analysis differentiation by polymerase chain reactionDavid J. Mancuso, Elodee A. Tuley, Lisa Westfield, Teresa L. Lester-Mancuso, Michelle M. Le Beau, James Sorace, Evan SadlerCite this: Biochemistry 1991, 30, 1, 253–269Publication Date (Print):January 1991Publication History Published online1 May 2002Published inissue 1 January...
Significance The blood protein von Willebrand factor (VWF) is required for platelets to stop bleeding at sites of injury, and the metalloprotease ADAMTS13 limits platelet adhesion by cleaving VWF only when flowing stretches it, especially within a growing thrombus. This feedback inhibition essential because deficiency causes fatal microvascular thrombosis. How recognizes so specifically not understood. We now find that folded roughly in half its distal domains inhibit domain. relieves this...
Deficiency of blood coagulation factor V or tissue causes the death mouse embryos by 10.5 days gestation, suggesting that part system is necessary for development. This function proposed to require either generation serine protease thrombin and cell signaling through protease-activated receptors an activity distinct from clotting. We find murine deficiency prothrombin clotting 2 (Cf2) was associated with approximately 50% Cf2 −/− embryonic day (E10.5), surviving had characteristic defects in...
The characterization of mutations in von Willebrand disease provides useful insight into the synthesis, structure, and function factor. This growing body information has prompted a reclassification vWD types that is intended to reflect distinct pathophysiologic mechanisms. Despite this apparent progress, many aspects vWF biology pathophysiology remain poorly understood. These include mechanism by which binding platelets induced at sites vascular injury, factors influence likelihood bleeding...
von Willebrand factor (VWF) is a multimeric plasma protein that mediates platelet adhesion to sites of vascular injury. The hemostatic function VWF depends upon the formation disulfide-linked multimers, which requires propeptide (D1D2 domains) and adjacent D'D3 domains. multimer assembly occurs in trans-Golgi at pH ~ 6.2 but not 7.4, suggests protonation one or more His residues (pK(a) ~6.0) dependence multimerization. Alignment 30 vertebrate sequences identified 13 highly conserved D1D2D'D3...
ADAMTS proteases typically employ some combination of ancillary C-terminal disintegrin-like, thrombospondin-1, cysteine-rich, and spacer domains to bind substrates facilitate proteolysis by an N-terminal metalloprotease domain. We constructed chimeric examine the role ADAMTS13 ADAMTS5 in recognition their physiological cleavage sites von Willebrand factor (VWF) aggrecan, respectively. cleaves Glu(373)-Ala(374) Glu(1480)-Gly(1481) bonds bovine aggrecan but does not cleave VWF. Conversely,...