Disease relevance of Cpa3

• After the adoptive transfer of V3 mast cells into BALB/c mice, v-abl-immortalized mast cells with mono- and multi-lobular nuclei were detected in the lymph nodes and other tissues of the mastocytosis mice that expressed c-kit, mMCP-5, mMCP-6, and mMC-CPA [1].
• Mast cell carboxypeptidase A has been isolated from the secretory granules of mouse peritoneal connective tissue mast cells (CTMC) and from a mouse Kirsten sarcoma virus-immortalized mast cell line (KiSV-MC), and a cDNA that encodes this exopeptidase has been cloned from a KiSV-MC-derived cDNA library [2].

High impact information on Cpa3

• The mast cells in the skeletal muscle that normally contain heparin lacked metachromatic granules and failed to store appreciable amounts of mouse mast-cell protease (mMCP)-4, mMCP-5 and carboxypeptidase A (mMC-CPA), even though they contained substantial amounts of mMCP-7 [3].
• Although these cultured cells contained high levels of various protease transcripts and had substantial amounts of mMCP-6 protein in their granules, they also failed to express mMCP-5 and mMC-CPA [3].
• Although rKL-developed BMMC were safranin+ and produced substantial amounts of 35S-labeled heparin proteoglycans, they contained only minimal amounts of histamine and MC-CPA enzymatic activity relative to serosal MC [4].
• Mouse serosal mast cells (SMCs) and Kirsten sarcoma virus-immortalized mast cells store large amounts of mast cell carboxypeptidase A and serine proteases in their secretory granules [5].
• The mature human MC-CPA enzyme has a predicted size of 36.1 kDa, a net positive charge of 16 at neutral pH, and 86% amino acid sequence identity with mouse MC-CPA [6].

Biological context of Cpa3

• When the mRNA expression of high-affinity IgE receptor beta-subunit and mast cell carboxypeptidase A was used as differentiation markers, the expression of these mRNAs continued even after the downregulation of GATA-2 expression [7].
• We have screened human lung cDNA libraries with a mouse mast cell carboxypeptidase A (MC-CPA) cDNA probe to isolate a near-full-length cDNA that encodes human MC-CPA [6].
• DNA blot analyses showed that human MC-CPA mRNA is transcribed from a single locus in the human genome [6].
• The Mc-cpa-/- mast cell phenotype was not associated with defects in degranulation in vitro or passive cutaneous anaphylaxis in vivo [8].
• The mMCP-6 and mMC-CPA genes are located on chromosomes 17 and 3, respectively, whereas the four mast cell chymase genes all reside on chromosome 14 linked to a gene complex that encodes four cytotoxic T lymphocyte granzymes [9].

Anatomical context of Cpa3

• The ear, skin, and purified serosal mast cells of WBB6F1/J-(+/+) (WB-(+/+)) and WCB6F1/J-(+/+) (WC-(+/+)) mice contain high steady-state levels of the transcripts that encode mouse mast cell protease (mMCP) 2, mMCP-4, mMCP-5, mMCP-6, and mouse mast cell carboxypeptidase A (mMC-CPA) [10].
• Mast cell carboxypeptidase A (Mc-cpa) is a highly conserved secretory granule protease [8].
• The mRNAs of MMCP-4 and mouse mast cell carboxypeptidase A were not expressed by mast cells in the stomach mucosa of untreated WBB6F1(-)+/+ mice but were expressed after the infection of Strongyloides venezuelensis [11].

Associations of Cpa3 with chemical compounds

• Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II [12].
• The deduced amino acid sequence revealed that, after cleavage of a 15-amino acid hydrophobic signal peptide and a 94-amino acid activation peptide from a 417-amino acid preproenzyme, the mature mast cell carboxypeptidase A protein core has a predicted Mr of 35,780 and a high positive charge [Lys + Arg) - (Asp + Glu) = 17) at neutral pH [2].
• Mouse mast cells differentially express at least four chymases (mouse mast cell protease (mMCP) 1, mMCP-2, mMCP-4, and mMCP-5), a tryptase (mMCP-6), and an exopeptidase (mouse mast cell carboxypeptidase A (mMC-CPA)) [9].
• With mast cell carboxypeptidase A, these serine proteases comprise the major proteins of mouse SMC secretory granules [5].
• 0. Microsequence analyses showed that two polypeptides of about 29 and 30 kDa had NH2 terminal amino acid sequences homologous to mouse MC proteinase 5 (MCP-5), whereas the amino terminals of the 33, 35, and 36 kDa proteins were homologous to MC carboxypeptidase A (MC-CPA) [13].

Other interactions of Cpa3

• A role for cathepsin E in the processing of mast-cell carboxypeptidase A [14].
• At least three proteins reacted with Abs to MC-CPA, whereas Abs to MCP-5 detected three adjacent polypeptides, rather than just the two identified by using microsequence analysis [13].

Analytical, diagnostic and therapeutic context of Cpa3

• Immunogold electron microscopy confirmed the granule location of mMC-CPA and mMCP-6 in both populations of cells, and cytochemical analysis confirmed the presence of chymotryptic enzymes in the granules [1].
• Thus, histochemistry and flow cytometry, commonly used to measure mast cell maturation, deviated from morphology in Mc-cpa-/- mice [8].
• The abolishment of c-kit mRNA expression appeared to be specific, because the expression of mast cell carboxypeptidase A mRNA but not of c-kit mRNA was detectable by in situ hybridization in skin mast cells of 5-day-old Wsh/Wsh mice [15].
• Isolation and molecular cloning of mast cell carboxypeptidase A. A novel member of the carboxypeptidase gene family [2].

References