Contact activation: a revision.
In conclusion, a revised view of the contact system has been presented. This system has little to do with the initiation of hemostasis. Like lupus anticoagulants, deficiencies of contact proteins give prolonged APTTs but may be risk factors for thrombosis. BK from kininogens is a potent modulator of vascular biology inducing vasodilation, tissue plasminogen activator release, and prostacyclin liberation. Kininogens, themselves, are selective inhibitors of alpha-thrombin-induced platelet activation preventing alpha-thrombin from cleaving the cloned thrombin receptor after arginine41. Kininogens' alpha-thrombin inhibitory activity exists in intact kininogens, BK, and all of BK's breakdown products. HK also is the pivotal protein for contact protein assembly on endothelium. It is the receptor for prekallikrein which when bound to HK becomes activated to kallikrein by an endothelial cell enzyme system independent of activated forms of plasma factor XII. Prekallikrein activation on endothelial cells results in kinetically favorable single chain urokinase and plasminogen activation. Thus the "physiologic, negatively charged surface" for contact system activation is really the assembly of these proteins on cell membranes and activation by membrane-associated enzymes.
Schmaier
A H
AH
Department of Internal Medicine, University of Michigan, Ann Arbor 48109-0724, USA. aschmaie@medmail.med.umich.edu
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000502:physiology; D004792:Enzyme Precursors / Q000502:physiology*; D005174:Factor XII / Q000502:physiology*; D006801:Humans; D007704:Kininogens / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011288:Prekallikrein / Q000502:physiology*; D013329:Structure-Activity Relationship
D004792:Enzyme Precursors; D007704:Kininogens; D005174:Factor XII; D011288:Prekallikrein