Production of the serum form of the transferrin receptor by a cell membrane-associated serine protease.

Recent investigations have demonstrated that the soluble form of the transferrin receptor in human serum is an 85-kDa fragment of intact receptor containing most of the extracellular domain. The recent demonstration of a remnant of the truncated receptor in cell membranes suggests that the soluble form arises from proteolytic cleavage of intact receptor. In the present investigation, domain-specific antibodies were used to further examine the subcellular location and nature of this proteolysis. HL60 cells were used in the investigation because the cells release an 85-kDa soluble form of the receptor to the culture supernatant that is identical to that found in serum. When intact, purified transferrin receptor from human placenta was incubated with the culture supernatant, no proteolytic activity could be demonstrated. However, when purified membrane fractions from HL60 cells were used in this incubation system, the 85-kDa fragment was produced. This activity was inhibited by serine protease inhibitors indicating that cell membrane fractions contain a serine protease capable of producing the serum form of the transferrin receptor.