One of the most exciting developments in the field of neuroendocrinology was the discovery last year that mammalian cells contain specialized proteinases homologous to the bacterial subtilisins. In contrast to the bacterial subtilisins, which show little sequence specificity, these new mammalian proteinases are remarkably specific and cleave exclusively at certain sets of basic residues. It now appears likely that this family of proteinases is responsible for the proteolytic activation of prohormones, neuropeptide precursors, and in all likelihood a wide variety of other protein precursors.

The fact that yeasts use a proteinase known as Kex2 to process the precursor to the α-factor pheromone has been accepted since the mid-80s (see review, Ref. 1). Since this yeast precursor is cleaved at pairs of basic residues, similar to the sites at which proinsulin as well as many other mammalian hormone and neuropeptide precursors are cleaved, it was long hypothesized that mammalian cells contain a homologous proteinase which is responsible for the paired basic cleavage event. Many laboratories tried without success to clone such mammalian enzymes from cDNA libraries using Kex2-based probes.