Molecular cloning of the mouse mast cell protease-5 gene. A novel secretory granule protease expressed early in the differentiation of serosal mast cells.
cDNAs were isolated that encode mouse mast cell protease-5 (MMCP-5), an approximately 30,000 Mr serine protease stored in the secretory granules of serosal mast cells (SMC) and Kirsten sarcoma virus-immortalized mast cells. Based on the deduced amino acid sequences of these cDNAs, MMCP-5 is synthesized as a 247-amino acid preproenzyme composed of a novel 19-residue hydrophobic signal peptide, a Gly-Glu activation peptide not present in other mast cell chymases, and a 226-amino acid protein that represents the mature enzyme. MMCP-5 possesses a unique Asn residue in the substrate binding cleft at residue 176 and is highly basically charged. The MMCP-5 gene was isolated, sequenced, and found to belong to a distinct subset of chymase genes. Allelic variations of the MMCP-5 gene were also detected. MMCP-5 is expressed in bone marrow-derived mast cells (BMMC), Kirsten sarcoma virus-immortalized mast cells, and SMC, but not in gastrointestinal mucosal mast cells of helminth-infected mice. The abundant levels of MMCP-5 mRNA in immature BMMC indicate that this chymase is expressed relatively early during the differentiation of mast cells. MMCP-5 is the first chymase to be molecularly cloned from progenitor mast cells and is also the first chymase shown to be expressed preferentially in the SMC subclass.
McNeil
H P
HP
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Austen
K F
KF
Somerville
L L
LL
Gurish
M F
MF
Stevens
R L
RL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D053818:Chymases; D003001:Cloning, Molecular; D003594:Cytoplasmic Granules / Q000201:enzymology*; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D008407:Mast Cells / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013379:Substrate Specificity; D016385:TATA Box; D014158:Transcription, Genetic
D004247:DNA; D012697:Serine Endopeptidases; D053818:Chymases