Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparin-deficient mice, generated by gene targeting of N-deacetylase/N-sulfotransferase-2 (NDST-2), display severe mast cell defects, including an absence of stored mast cell proteases. However, the mechanism behind these observations is not clear. Here we show that NDST-2+/+ bone marrow-derived mast cells cultured in the presence of IL-3 synthesise, in addition to highly sulphated chondroitin sulphate (CS), small amounts of equally highly sulphated heparin-like polysaccharide. The corresponding NDST-2-/- cells produced highly sulphated CS only. Carboxypeptidase A (CPA) activity was detected in NDST+/+ cells but was almost absent in the NDST-/- cells, whereas tryptase (mouse mast cell protease 6; mMCP-6) activity and antigen was detected in both cell types. Antigen for the chymase mMCP-5 was detected in NDST-2+/+ cells but not in the heparin-deficient cells. Northern blot analysis revealed mRNA expression of CPA, mMCP-5 and mMCP-6 in both wild-type and NDST-2-/- cells. A approximately 36 kDa CPA band, corresponding to proteolytically processed active CPA, as well as a approximately 50 kDa pro-CPA band was present in NDST-2+/+ cells. The NDST-2-/- mast cells contained similar levels of pro-CPA as the wild-type mast cells, but the approximately 36 kDa band was totally absent. This indicates that the processing of pro-CPA to its active form may require the presence of heparin and provides the first insight into a mechanism by which the absence of heparin may cause disturbed secretory granule organisation in mast cells.
 ...
PMID:Altered storage of proteases in mast cells from mice lacking heparin: a possible role for heparin in carboxypeptidase A processing. 1210 44

Carboxypeptidase A (CPA) is a metalloprotease, residing in the mast cell secretory granules together with chymases and tryptases. Little information is available with respect to the mechanisms that maintain or regulate the levels of stored proteases in the mast cell secretory granules. In this study we examined whether cathepsins C and S may be involved in the control of the levels of mast cell proteases. Mast cells cultured from bone marrow of cathepsin C- or S-null mice expressed higher levels of CPA protein and activity than cells from wild-type mice. Similar increases in protein were observed for the mouse chymase, mast cell protease-5 (mMCP-5), but not for the tryptase, mMCP-6. Steady-state levels of CPA and mMCP-5 mRNA were similar in wild-type and cathepsin C-null mast cells, indicating that post-transcriptional mechanisms explain the observed cathepsin C-dependence of CPA and mMCP-5 expression. The present study thus indicates novel roles for cathepsins C and S in regulating the levels of stored proteases in the mast cell secretory granules.
 ...
PMID:Mast cell cathepsins C and S control levels of carboxypeptidase A and the chymase, mouse mast cell protease 5. 1466 96

Carboxypeptidase A and carboxypeptidase B activities from the midgut of Trichoplusia ni larvae were characterized. In the T. ni larval midgut, the primary digestive carboxypeptidase activity was attributed to carboxypeptidase A, which was eight times more active than carboxypeptidase B. Both the midgut carboxypeptidase A and carboxypeptidase B exhibited maximal activities at pH 8.0-8.5 and were similarly susceptible to inhibition by potato carboxypeptidase inhibitor and phenanthroline. The midgut carboxypeptidase activities were analyzed in T. ni larvae fed on various diet sources and the results indicated that midgut carboxypeptidase activities per milligram of gut were similar regardless of the amount of dietary proteins or amino acids. However, midgut carboxypeptidase A activity was significantly higher in larvae exposed to soybean trypsin inhibitor and was significantly lower in larvae fed on broccoli foliage. From the T. ni larval midgut, five putative carboxypeptidase cDNAs were cloned, demonstrating that midgut carboxypeptidase activities are composed of multiple carboxypeptidase types. Sequence analysis indicated that the midgut carboxypeptidases were produced as secreted proenzymes which could be activated after removal of an N-terminal activation fragment by a trypsin. Two cloned cDNAs are predicted to code for carboxypeptidase A and one cDNA is predicted to code for a putative carboxypeptidase B. The other two cDNAs are highly similar to carboxypeptidase A and carboxypeptidase B in sequences, but their activity was not predictable.
 ...
PMID:Characterization and cDNA cloning of midgut carboxypeptidases from Trichoplusia ni. 1526 87


<< Previous 1 2