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JBC, Vol. 252, Issue 17, 6097-6104, Sep, 1977
R. Mandle Jr and A. P. Kaplan
Two molecular forms of prekallikrein can be isolated from pooled normal
human plasma. Their approximate molecular weights by sodium dodecyl
sulfate-gel electrophoresis are 88,000 and 85,000. The two bands observed
are shown to represent prekallikrein by functional, immunochemical, and
structural criteria. Both forms are cleaved by activated Hageman factor,
they appear to share antigenic determinants, they are not interconvertible
upon incubation with activated Hageman factor or kallikrein, and the ratio
of kinin-generating, and plasminogen-activating activities of the
preparations are independent of the relative proportion of each band.
Activated Factor XII converts prekallikrein to kallikrein by limited
proteolysis and two disulfide-linked chains designated kallikrein heavy
chain (Mr = 52,000) and kallikrein light chains (Mr = 36,000 or 33,000) are
formed. The active site is associated with the light chains as assessed by
incorporation of [3H]diisopropyl fluorophosphate. No dissociable fragments
were observed in the absence of reducing agents. However, kallikrein could
digest prekallikrein to diminish its molecular weight by 10,000. In
addition, two factors capable of activating plasminogen to plasmin have
been isolated; one is identified as kallikrein. The second principle
fractionates with Factor XI and is demonstrable in normal and
prekallikrein-deficient plasma.
Hageman factor substrates. Human plasma prekallikrein: mechanism of activation by Hageman factor and participation in hageman factor-dependent fibrinolysis
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