Post-translational modification of peptide messengers in the gut

Recombinant DNA technology has enabled valuable information to be obtained on the precursors of gastrointestinal regulatory peptides. A number of precursors such as progastrin and proCCK contain a single recognized biologically active sequence, while others contain multiple active sequences. Some of the latter group such as proenkephalin contain repeated copies of a single peptide sequence, some such as proVIP and proglucagon contain related, but not identical, biologically active peptides, and others such as proopiomelanocortin contain unrelated active sequences. However, while cDNA sequencing studies reveal the potential secretory products available within precursors, they provide no information on the actual cleavages and prosthetic modifications that occur. Some prediction of processing events can be made from the occurrence of consensus sequences of amino acids, but confirmation is possible only by isolation and characterization of the products of the post-translational processing. This is of particular physiological significance because in many instances processing occurs in a cell-specific manner, such that a single precursor may give rise to several products with a range of biological activities. For this reason it is important that studies of post-translational processing keep pace with the ever increasing number of precursor sequences deduced by recombinant DNA technology.