Further evidence for the mitogenic action of urinary trypsin inhibitor

We have previously shown that urinary trypsin inhibitor (UTI), also known and bikunin, was mitogenic for human fibroblasts at low concentrations, and growth-inhibitory at higher concentrations, and have identified high- and low-affinity cellular binding sites for this protein. We have now investigated fibroblast proteins which interact with bikunin. Bikunin binds to proteins of about 50K and 250K. The simplest interpretation, is that the 50K protein may be a proteinase which is also the low-affinity bikunin binding site, involved in growth inhibition, and that the larger protein may be responsible for the mitogenic response to bikunin. Inhibitors of intracellular calcium mobilisation also inhibit the mitogenic response to bikunin, and by the measurement of the efflux of pre-loaded 45Ca2+, bikunin at mitogenic concentrations can be shown to stimulate calcium mobilization.