Phospholipid composition controls thromboplastin sensitivity to individual clotting factors

Protein-phospholipid interactions in blood clotting.

Most steps of the blood clotting cascade require the assembly of a serine protease with its specific regulatory protein on a suitable phospholipid bilayer. Unfortunately, the molecular details of how blood clotting proteins bind to membrane surfaces remain poorly understood, owing to a dearth of techniques for studying protein-membrane interactions at high resolution. Our laboratories are tackl...

Fibroblastoid and epithelioid cells in tissue culture: differences in sensitivity to ouabain and to phospholipid composition.

Investigations on nine different mammalian cell lines revealed that permanently growing cells of one morphological class have numerous membrane properties in common which are different or even lacking in the other cell class. With electrophysiological methods it is shown that the sensitivity of the Na<·K< pump to ouabain is three orders of magnitude higher in the ionically non· coupled epitheli...

Recombinant clotting factors.

The recombinant era for haemophilia began in the early 1980s with the cloning and subsequent expression of functional proteins for both factors VIII and IX. Efficient production of recombinant clotting factors in mammalian cell culture systems required overcoming significant challenges due to the complex post-translational modifications that were integral to their pro-coagulant function. The qu...

The local phospholipid environment modulates the activation of blood clotting.

Examples abound of membrane-bound enzymes for which the local membrane environment plays an important role, including the ectoenzyme that triggers blood clotting, the plasma serine protease, factor VIIa, bound to the integral membrane protein, tissue factor. The activity of this enzyme complex is markedly influenced by lipid bilayer composition and further by tissue factor partitioning into mem...

Nomenclature for blood clotting factors.