Aminopeptidase A

Abstract

Aminopeptidase A (APA) is expressed in mice on early B lineage cells and on a population of thymic cortical epithelial cells, but not on mature lymphocytes. IL-7 has been shown to selectively induce the APA expression on pre-B cells coincident with their growth. The expression on bone marrow stromal cell lines correlates with their ability to support growth of B lineage cells. APA is a disulfide-linked homodimer of a type II integral membrane protein. The extracellular region contains a typical zinc binding motif. Human APA shows sequence similarity to human CD13 (aminopeptidase N or APN). The molecule can be phosphorylated. APA is a zinc-dependent metallopeptidase that cleaves N-terminal Glu or Asp residues from peptides. In mice, the BP-1 mAb blocks APA enzymatic activity and inhibits IL-7-driven proliferation of pre-B cells in the context of the bone marrow microenvironment, but does not inhibit the growth of purified pre-B cells in response to IL-7. This suggests that APA cleaves, and inactivates, a peptide that serves as a natural inhibitor of B cell precursor proliferation.