Human eosinophil cationic protein. Molecular cloning of a cytotoxin and helminthotoxin with ribonuclease activity.
We have isolated a 725-bp full-length cDNA clone for the human eosinophil cationic protein (ECP). ECP is a small, basic protein found in the matrix of the eosinophil's large specific granule that has cytotoxic, helminthotoxic, and ribonuclease activity, and is a member of the ribonuclease multigene family. The cDNA sequence shows 89% sequence identity with that reported for the related granule protein, eosinophil-derived neurotoxin (EDN). The open reading frame encodes a previously unidentified 27-amino acid leader sequence preceding a 133-residue mature ECP polypeptide with a molecular mass of 15.6 kD. The encoded amino acid sequence of ECP shows 66% identity to that of EDN and 31% identity to that of human pancreatic ribonuclease, including conservation of the essential structural cysteine and cataytic lysine and histidine residues. mRNA for ECP was detected in eosinophil-enriched peripheral granulocytes and in a subclone of the promyelocytic leukemia line, HL-60, induced toward eosinophilic differentiation with IL-5. No ECP mRNA was detected in uninduced HL-60 cells, or in HL-60 cells induced toward monocytic differentiation with vitamin D3 or toward neutrophilic differentiation with DMSO. In contrast, mRNA for EDN was detected in uninduced HL-60 cells and was upregulated in HL-60 cells induced with DMSO. Despite similarities in sequence and cellular localization, these results suggest that ECP and EDN are subject to different regulatory mechanisms.
Rosenberg
H F
HF
Division of Infectious Diseases, Harvard Medical School, Boston, Massachusetts.
Ackerman
S J
SJ
Tenen
D G
DG
D000595:Amino Acid Sequence; D000871:Anthelmintics; D001483:Base Sequence; D001798:Blood Proteins / Q000235:genetics* / Q000502:physiology; D015152:Blotting, Northern; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D003603:Cytotoxins; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000378:metabolism*; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000097:blood / Q000235:genetics; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic
D000871:Anthelmintics; D001798:Blood Proteins; D003603:Cytotoxins; D047091:Eosinophil Granule Proteins; D012313:RNA; D012260:Ribonucleases