Hematopoietic differentiation antigens that are membrane-associated enzymes: cutting is the key!

Abstract

ANY CELL SURFACE glycoproteins expressed dur-M ing specific stages of lymphoid and myeloid cell development were initially characterized on the basis of their reactivity with monoclonal antibodies (MoAbs). Subsequent analysis of cloned cDNAs identified four of these hematopoietic differentiation antigens as membrane-associated enzymes with common structural and regulatory features: CDlO/neutral endopeptidase 24.11 (CDlO/NEP), CD 13/aminopeptidase N (CD 13/APN), BP-1 /6C3/aminopeptidase A (BP-1 /6C3/APA), and CD26/dipeptidyl peptidase IV (CD26/DPPIV).'-9 All four of these enzymes are type I1 integral membrane proteins with a single hydrophobic sequence that functions as both a signal peptide and a transmembrane region.'-' Three of these enzymes (CD10/ NEP, CD 1 3/APN, and BP-1 /6C3/APA) require zinc for biologic activity and share a pentapeptide consensus sequence that has been implicated in both zinc binding and catalys ~s . ~, ~, ' Although CDlO/NEP, CD13/APN, BP-l/6C3/APA, and CD26/DPPIV are expressed by different hematopoietic cell types at unique stages of lymphoid or myeloid differentiation, they are coexpressed on the luminal surface of epithelial brush borders. All four enzymes participate in the final stages of peptide hydrolysis in the renal proximal tubules and the small intestine. In certain instances, these enzymes also work in concert to digest common substrates.*-l2 CD73/ecto 5'-nucleotidase is another hematopoietic differentiation antigen and cell surface enzyme that is also expressed on epithelial brush borders. A glycosyl phosphotidylinositol-linked protein, CD73/ESN, differs from the above-mentioned enzymes in its transmembrane orientation and its role in nucleoside dephosphorylation and trans-The well-characterized activities of these enzymes in non-~0 r t .