Structural and immunological homology of human and porcine pituitary and plasma IRCM-serine protease 1 to plasma kallikrein: marked selectivity for pairs of basic residues suggests a widespread role in pro-hormone and pro-enzyme processing.
IRCM-serine protease 1 (SP1), originally isolated from porcine pituitaries and exhibiting preference for cleavage at pairs of basic residues has now been isolated in sufficient quantities to be structurally characterized from both porcine and human pituitaries and plasmas. Whereas the porcine protease shows a high degree of amino acid sequence homology to human plasma pre-kallikrein, the human homologue exhibits an identity of sequence in the first 25 residues of each chain (regulatory and catalytic chains). In addition, human plasma and pituitary IRCM-SP1 and human plasma pre-kallikrein show virtually identical immunological and molecular properties. These data strongly suggest that IRCM-SP1 and plasma pre-kallikrein originate from the same gene product. Purified extracts from perfused rat pituitaries show that 32% of the IRCM-SP1 activity found in normal rat pituitaries, still remain. These data together with the demonstrated association of IRCM-SP1 with particulate fractions of the pituitary suggest that IRCM-SP1 represents a tissue form of plasma pre-kallikrein. The characterization of the digestion products obtained upon reaction of IRCM-SP1 with pro-insulin, ACTH1-39, pro-dynorphin and pro-enkephalin-derived peptides, somatostatin-28, and a pro-renin-like peptide confirmed the high degree of cleavage selectivity of this enzyme for pairs of basic residues.
Seidah
N G
NG
Clinical Research Institute of Montreal, Quebec, Canada.
Paquin
J
J
Hamelin
J
J
Benjannet
S
S
Chretien
M
M
D000595:Amino Acid Sequence; D000818:Animals; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics*; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D007610:Kallikreins / Q000097:blood / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010902:Pituitary Gland / Q000201:enzymology*; D010903:Pituitary Gland, Anterior / Q000201:enzymology; D011288:Prekallikrein / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D011919:Rats, Inbred Strains; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000097:blood / Q000235:genetics* / Q000302:isolation & purification; D013045:Species Specificity; D013552:Swine; D014357:Trypsin / Q000378:metabolism
D004792:Enzyme Precursors; D011288:Prekallikrein; C048880:IRCM-serine protease 1; D007610:Kallikreins; D012697:Serine Endopeptidases; D014357:Trypsin; D005341:Fibrinolysin