Disease relevance of Mcpt4

• A comparison with the corresponding region of the rat mucosal mast cell-specific protease RMCP-II is presented. cDNA clones for the mast cell proteases MMCP-4 (950 bp) and MMCP-5 (1098 bp) were isolated from a cDNA library of a connective tissue mast cell-like mouse mastocytoma cell line [1].
• Intradermal injection of mMCP-4 not only induced skin edema but increased MIP-2 content and neutrophil number at the injection site [2].
• The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4) [3].

High impact information on Mcpt4

• To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties [4].
• The inactivation of mMCP-4 did not affect the storage of other mast cell proteases and did not affect the number of mast cells or the mast cell morphology [4].
• Further, a role for mMCP-4 in connective tissue remodeling was suggested by the inability of mMCP-4 null peritoneal cells to process endogenous fibronectin [4].
• However, mMCP-4 inactivation resulted in complete loss of chymotryptic activity in the peritoneum and in ear tissue, indicating that mMCP-4 is the main source of stored chymotrypsin-like protease activity at these sites [4].
• The mMCP-4 null cells showed markedly impaired ability to perform inactivating cleavages of thrombin, indicating a role for mMCP-4 in regulating the extravascular coagulation system [4].

Biological context of Mcpt4

• Deficient transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype [5].
• The overexpression of the normal (+) MITF but not of mi-MITF normalized the poor expression of the MMCP-4 gene in mi/mi CMC, indicating the involvement of +-MITF in transactivation of the MMCP-4 gene [5].
• Using a cDNA probe derived from the 3'-untranslated portion of the MMCP-4 cDNA, the gene for MMCP-4 and a second highly related gene (mouse mast cell protease-like, MMCP-L) were cloned from a BALB/c mouse genomic DNA library and sequenced entirely, including approximately 2 kilobases of the 5'-flanking region [6].
• MMCP-4 and MMCP-L have five exons of identical length, four introns of nearly identical length, and approximately 900 base pairs of 5'-flanking DNA with sequence similarity by dot matrix analysis [6].
• Gastric mast cells showed a phenotype related to connective-type mast cells, since they were stained by safranin, and strong expression of mouse mast cell protease-4 and -5 was found in this organ [7].

Anatomical context of Mcpt4

• They did not contain MMCP-4 or -2 mRNA, genes expressed late in the differentiation of progenitor cells into serosal and mucosal MCs, respectively [8].
• Cloning of the cDNA and gene for mouse mast cell protease 4. Demonstration of its late transcription in mast cell subclasses and analysis of its homology to subclass-specific neutral proteases of the mouse and rat [6].
• MMCP-4 is the first secretory granule serine protease of CTMC to be molecularly cloned [6].
• Furthermore, the peritoneal mast cells did not change the MMCP-4 and MMCP-6 mRNA expression phenotype after the settlement in either the mucosa or the muscularis propria of WBB6F(1)-W/Wv mice [9].
• SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site [3].

Associations of Mcpt4 with chemical compounds

• In the mMCP-4(-/-) cell cultures no reduction in the rate of Ang II generation was seen, but the formation of Ang-(5-10) was completely abrogated [10].
• Cooperation between mast cell carboxypeptidase A and the chymase mouse mast cell protease 4 in the formation and degradation of angiotensin II [10].
• Histological analysis revealed an increase in collagen in the ear tissue of mMCP-4-deficient animals accompanied by increased ear thickness and a higher content of hydroxyproline [11].
• These properties match those of chymase, but unlike chymase, myonase does not interact with heparin in the regulation of its activity [12].
• Myonase is completely inhibited by such serine proteinase inhibitors as chymostatin, diisopropylfluorophosphate and phenylmethylsulfonyl fluoride, but not by p-tosyl-L-phenylalanine chloromethyl ketone, p-tosyl-L-lysine chloromethyl ketone, pepstatin, E-64, EDTA, and o-phenanthroline [12].

Other interactions of Mcpt4

• Biochemical and immunological characterization of multiple glycoforms of mouse mast cell protease 1: comparison with an isolated murine serosal mast cell protease (MMCP-4) [13].
• Evidence for at least two additional, but not so recent, exchanges was found in the 3' regions of the MMCP-4 and MMCP-L genes and in the 5' regions of the genes for MMCP-1 and MMCP-2 [14].
• We compared the regulation mechanisms of another chymase, MMCP-4, with those of MMCP-5 and MMCP-6 [5].
• MMCP-4 mRNA was not expressed in normal mouse intestine or in interleukin 3-dependent bone marrow-derived mast cells, which can serve as precursors to both MMC and CTMC [6].
• The expression of MMCP-2, MMCP-4, and MMCP-6 was much greater in IC-2G559 and IC-2V814 cells than in the original IC-2 cells [15].

Analytical, diagnostic and therapeutic context of Mcpt4

• N-terminal sequence analysis of the purified protein demonstrated 100% identity of the thrombin-inactivating serine protease with the secretory granule chymases: murine mast cell protease 3 and murine mast cell protease 4 [16].
• An in situ hybridization study confirmed the higher expression of mouse mast cell protease-4 by connective-tissue-type mast cells in tight-skin skin than Pallid skin [17].
• Age-matched (10-wk-old) tight-skin and Pallid were quantified for their mRNA of connective-tissue-type mast-cell-specific chymase, mouse mast cell protease-4, by the competitive reverse transcriptase polymerase chain reaction technique, which revealed its higher level in tight-skin than Pallid [17].
• Western blots and immunohistochemical analyses showed that myonase was present within myocytes of both MDX-mouse and control mouse, and subcellular fractionation showed that it was associated with myofibrils [18].
• The molecular mass of the purified myonase was determined to be 26 kDa by SDS-PAGE and to be 25,187 Da by mass spectrometry [12].

References