ArticleInsect biochemistry and molecular biology2025
CLIPA protein pairs function as cofactors for prophenoloxidase activation in Anopheles gambiae.
Article in Insect biochemistry and molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Partial reconstitution of the prophenoloxidase activation system inProceedings of the National Academy of Sciences of the United States of America · 2026Article
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Abstract
Insect prophenoloxidases (proPO) are activated during immune responses by a proPO activating protease (PAP) in the presence of a high molecular weight cofactor assembled from serine protease homologs (SPH) that lack proteolytic activity. PAPs and the SPHs have a similar architecture, with an amino-terminal clip domain and a carboxyl-terminal protease domain. The SPHs belong to CLIPA subfamily of SP-related proteins. In Manduca sexta, a well characterized biochemical model system for insect immunity, the functional SPH cofactor contains one molecule each from two SPH subfamilies, SPH-I and SPH-II. In Anopheles gambiae, three SPHI-SPHII pairs (CLIPs A4-A6, A4-A7Δ, and A4-A12) were previously reported as cofactors for CLIPB9-mediated activation of proPO2 and proPO7. In this study, we produced recombinant proteins for two splicing variants of CLIPA7, proCLIPA7s (s for short), proCLIPA7f (f for full-length) and proCLIPA14. We cleaved each along with proCLIPA4 using M. sexta PAP3 and found that the CLIPA pairs A4-A7s and A4-A14 are better than A4-A7f in generating highly active PO2 or PO7. CLIPA7f and CLIPA7s, products of alternative splicing, have different strengths as cofactors in combination with CLIPA4. Because mRNA for CLIPA7f is expressed at a significantly higher level than CLIPA7s, cofactors with the weaker combination A4-A7f may predominate in hemolymph, resulting in a potential dampening effect on proPO activation as a regulatory mechanism for altering the strength of the melanization response. A. gambiae CLIPB10x
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