The fluid phase inactivation of C2hu by C1hu is markedly enhanced by the presence of C4hu. The enhancement is afforded by C1 inactivated C4hu, namely C4ihu, and requires the simultaneous presence of enzymatically active C1. Heterologous C4 of guinea pig origin protects C2hu from the inactivation by C1hu. Thus, in both the fluid phase and on the cellular intermediate, C4hu is essential to the specific action of C1hu on C2hu. It is possible that C4i alters C2 so as to present a more suitable substrate to the C1 enzyme or that C4i acts on the C1 to uncover a specificity for native C2.
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