title: Substrate specificities of murine C1s.
abstract: An early step in the initiation of the classical C pathway is the proteolytic activation of component C4 by subcomponent C1-s. We have examined the substrate specificity of murine C1-s (mC1-s) by measuring its proteolytic activity on human and murine C4, and on the murine C4 isotype designated sex-limited protein (Slp). The latter substrate was examined because previous studies have demonstrated that Slp is not cleaved by C1-s, and hence Slp has been assumed to be nonfunctional in the C pathways. Those earlier studies used human, not murine, C1-s, however; a recent report has suggested that Slp is an essential component of a novel complement activation pathway and that the previous failure to observe cleavage of Slp is probably the result of a species incompatibility between Slp and the heterologous human C1-s (hC1-s). The present studies do not support this idea, as we found no evidence of cleavage of Slp by homologous murine C1-s even at enzyme concentrations 10-fold higher than that necessary for 50% cleavage of murine C4 (mC4). We did find a species-specific affect in the cleavage of mC4, where mC1-s is about 10-fold more effective than heterologous hC1-s in cleaving mC4, but mC1-s itself does not distinguish between human and murine C4, cleaving both equally well. Hence mC1-s does not exhibit the species specificity previously found for hC1-s, which shows a several hundred-fold preference for homologous human C4 over murine C4.
authors.affiliation: Medical Biology Institute, La Jolla, CA 92037.
authors.forename: R T
authors.initials: RT
authors.lastname: Ogata
authors.forename: P J
authors.initials: PJ
authors.lastname: Low
authors.forename: B M
authors.initials: BM
authors.lastname: Bradt
authors.forename: N R
authors.initials: NR
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism; D003173:Complement C1s / Q000378:metabolism*; D003181:Complement C4 / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D001798:Blood Proteins; C018386:C4a protein, mouse; D003181:Complement C4; D003173:Complement C1s