Characterization of a novel, human cytotoxic lymphocyte-specific serine protease cDNA clone (CSP-C).
A human cDNA clone encoding a novel serine protease, cytotoxic serine protease-C(CSP-C), has been isolated from a cDNA library prepared from recombinant interleukin-2 (IL-2)-activated lymphocytes of a patient with a large granular lymphoproliferative disorder. The clone has a 741-base pair open reading frame encoding a putative 246-amino acid protein. The protein sequence contains the catalytic charge relay system characteristic of a serine protease and the conserved N-terminal amino acid sequence of the mature cytotoxic lymphocyte serine proteases found in both mouse and human. The amino acid sequence of CSP-C has 71% identity with the previously reported cytotoxic serine protease-B(CSP-B)/human lymphocyte protease (HLP)/SECT and 57% identity with the granulocyte-specific serine protease cathepsin G. The homology with another lymphocyte-specific serine protease, human Hanukah factor (HF)/Granzyme A was 41%. The transcript is expressed in lymphocytes stimulated with IL-2 or IL-2 plus phytohemagglutinin (PHA). CSP-C is not expressed in B-lymphoblastoid cell lines or in the T-leukemia cell line MOLT4. The cDNA sequence suggests that the protein is expressed as a prepropeptide, as has been found in the other murine and human serine proteases of lymphocyte origin. It has recently been reported that human chromosome 14q11, in addition to containing the genes encoding cytotoxic serine protease B (CSP-B), cathepsin G, and the T-cell receptor alpha and delta genes, also includes an additional genomic DNA clone which cross-hybridized with CSP-B and cathepsin G, cathepsin-like gene-2 (CGL-2). It is likely that the CSP-C cDNA clone reported in this study corresponds to CGL-2.
Laboratory of Human Immunogenetics, Memorial Sloan-Kettering Cancer Center, New York, New York.
J L
JL
Klein
A
A
Selvakumar
J A
JA
Trapani
B
B
Dupont
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D015973:Gene Expression Regulation, Leukemic / Q000235:genetics; D015723:Gene Library; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000201:enzymology; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008232:Lymphoproliferative Disorders / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology
D007376:Interleukin-2; D012333:RNA, Messenger; D004247:DNA; D012697:Serine Endopeptidases; C057818:cytotoxic T lymphocyte-specific serine protease