The immunoglobulin domain of C. elegans IGEG-2/EGF is required for its function.

Epidermal Growth Factor (EGF) family ligands mediate signaling events in development and physiology across species. These ligands are transmembrane proteins that undergo ectodomain shedding to release the soluble EGF domain, which mediates interaction with EGF receptors (EGFR). Some EGF ligand ectodomains also contain an immunoglobulin-like domain (IgD), and the function of this domain within Ig-EGFs varies. C. elegans IGEG-2 is an EGFR ligand of unknown function, identified and named for its Ig and EGF domains. The EGF domain appears to be functional, as widespread expression of IGEG-2 produces phenotypes associated with EGFR hyperactivation. Here we use these phenotypes to investigate the contribution of the IGEG-2 IgD, and we find it to be essential for IGEG-2 /EGF signaling. The mechanism underlying this strict IgD dependence is not known.