Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 (enkephalinase): direct evidence by cDNA transfection analysis

摘要: Abstract The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most leukemias, certain other lymphoid malignancies with an immature phenotype, and normal progenitors. A computer search against the recent GenBank release (no. 56) indicates that human CALLA cDNA encodes nearly identical to rat rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopeptidase, which has been shown inactivate variety of peptide hormones including enkephalin, chemotactic peptide, substance P, neurotensin, oxytocin, bradykinin, angiotensins I II, had not identified in cells. To determine whether derived from cells (Nalm-6 cell line) functional activity, we generated CALLA+ stable transfectants CALLA- murine myeloma line J558 analyzed them for enzymatic activity fluorometric assay based upon cleavage substrate glutaryl-Ala-Ala-Phe 4-methoxy-2-naphthylamide at Ala-Phe bond. Total lysates as well whole-cell suspensions Nalm-6 transfectants, but cells, possessed activity. was associated cellular fraction abrogated specific inhibitor phosphoramidon. The unequivocal identification provides insight into its potential role both malignant function.