Transforming growth factor-βs and related gene products in mosquito vectors of human malaria parasites: Signaling architecture for immunological crosstalk

The participation of a divergent mosquito transforming growth factor-β (TGF-β) and mammalian TGF-β1 in the Anopheles stephensi response to malaria parasite development [Infect. Genet. Evol. 1 (2001) 131-141; Infect. Immun. 71 (2003) 3000-3009] suggests that a network of Anopheles TGF-β ligands and signaling pathways figure prominently in immune defense of this important vector group. To provide a basis for identifying the roles of these proteins in Anopheles innate immunity, we identified six predicted TGF-β ligand-encoding genes in the Anopheles gambiae genome, including two expressed, diverged copies of 60A, the first evidence of ligand gene duplication outside of chordates. In addition to five predicted type I and II receptors, we identified three Smad genes in the A. gambiae genome that would be predicted to support both TGF-β/Activin- and bone morphogenetic protein (BMP)-like signaling. All three Smad genes are expressed in an immunocompetent A. stephensi cell line and in the A. stephensi midgut epithelium, confirming that a conserved signaling architecture is in place to support signaling by divergent exogenous and endogenous TGF-β superfamily proteins.