A motif found in propeptides and prohormones that may target them to secretory vesicles

Sorting of prohormones and propeptides into secretory vesicles at the trans-Golgi face probably depends on a signal contained within the amino acid sequence of the peptide. To date no consensus sequence has been identified in prohormones or propeptides that might serve such a targeting function. In this report, we have analyzed the amino acid sequences and secondary structures of 15 prohormones and propeptides that have been shown experimentally to be sorted to secretory vesicles when the corresponding cDNA is transfected into mouse pituitary AtT20 cells. From these analyses, we have identified a motif that is shared by all of these diverse propeptides and might serve as a vesicular targeting sequence. This motif is degenerate and consists of two or more leucines occupying one side of a highly amphipathic α-helix with a serine (or rarely threonine) positioned N-terminal to the leucines and projecting to the same side of the helix.