Background of the antigen
Guanine nucleotide-exchange proteins (GEPs) accelerate replacement of bound GDP with GTP and thereby activate ADP-ribosylation factors (ARFs), a family of guanine nucleotide-binding proteins that play an important role in intracellular vesicular trafficking. GEPs comprise two major families, large GEPs that are inhibited by brefeldin A (BFA), a protein that effects golgi structure, and a group of smaller GEPs that are insenstive to BFA. Two genes for GEPs found on human chromosomes 8 and 20 encode BFA sensitive GEPs designated BIG1 and BIG2. Both GEPS contain a sec7 domain that is responsible for their brefeldin inhibition and also their catalytic activity. In vivo, BIG1 and BIG2 exist in macromolecular complexes that move between the golgi membranes and cytosol. BIG2 associates with PKA regulatory subunits, implying that BIG2 may act as an A kinase-anchoring protein (AKAP) that could coordinate the cAMP and ARF regulatory pathways.
