Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD23 is a multifunctional molecule expressed by cells of lymphoid, myeloid and hematopoietic lineages. As a cell surface molecule CD23 acts both as a low-affinity receptor for IgE (Fc epsilon RII) and as a cell adhesion molecule. CD23 can undergo autoproteolysis to release soluble 37-25-kDa CD23 (s-CD23) molecules with a range of cytokine activities. Here we show a causal link between the two apparently disparate functions of autoproteolysis and cell adhesion. The Epstein-Barr virus-transformed B cell line RPMI-8866 formed macroscopic cell clusters solely via CD23. Cell adhesion was inhibited by mAb to CD23 and by IgE. Cell adhesion was also dependent on serum as cells grown in serum-free media failed to form clusters. In serum-free conditions cell adhesion could be induced by the addition of not only 10% FCS but also s-CD23. As s-CD23 is reported to possess proteolytic activity we screened a range of proteases to determine whether they also could induce cell adhesion in serum-free medium. It was found that chymotrypsin and elastase induced cell:cell adhesion in RPMI-8866 cells. The same panel of proteases were screened against a range of CD23-positive (Jijoye, AF-10, T2, U937, ICH-1) and CD23-negative (RPMI-8226, U266, MOLT-4, Ramos) cell lines. It was found that chymotrypsin and elastase induce cell adhesion only in cells expressing CD23. Peptide mapping studies showed that chymotrypsin and elastase cleaved immunoprecipitated CD23 near the same site by which 37-kDa s-CD23 is released (Ala 80). Serum demonstrated no proteolytic activity towards CD23. However, it was found that cells grown in serum-free medium released 25-kDa s-CD23 without the need for prior cleavage at the 37-kDa cleavage site. To confirm the role of proteolysis in CD23-mediated cell adhesion we screened a range of protease inhibitors for their ability to antagonize this process. It was found that tosyl-lysine chloromethyl ketone inhibited CD23-mediated cell adhesion. Lactoperoxidase treatment, which inhibits CD23 cleavage, also inhibited cell adhesion. Addition of chymotrypsin and elastase to lactoperoxidase-treated cells induced cell adhesion. From these data we propose that intact CD23 has no demonstrable role in cell adhesion; instead, the portion of CD23 remaining on the cell surface following cleavage appears to mediate cell adhesion.
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PMID:CD23-mediated homotypic cell adhesion: the role of proteolysis. 837 Mar 88

epsilon receptor modulating protein (epsilon RMP) was identified and purified in our previous studies as a murine T cell-derived soluble 17-kDa chymotryptic serine protease which suppresses avidity of binding between IgE and CD23 (low affinity Fc receptor for IgE) without decreasing the quantitative expression of the CD23 molecule. Some, but not all, of the other known soluble serine proteases showed epsilon RMP-like CD23-modulating activities. Further studies indicated that epsilon RMP exists not only as a soluble protein but also as a 36-kDa T-cell surface form. Both soluble and membrane-bound epsilon RMP can induce purified splenic B cells to secrete IgE in the presence of IL-4 even without lipopolysaccharide (LPS). In this study, therefore, we have tested effects of several known serine proteases on Ig production in vitro and have found that: (i) coculture of splenic B cells in the presence of LPS and IL-4 with serine proteases which have epsilon RMP-like substrate specificity, such as kallikrein and alpha-chymotrypsin, results in a significant increase of IgG1 and a slight increase of IgE secretion at low concentrations, and significant suppression at high concentrations in an isotype-selective manner; and (ii) the effects of these proteases are blocked by phenylmethylsulfonyl fluoride but not by indomethacin, suggesting that serine protease activity but not prostaglandin E2 is involved. The biological significance of the possible involvement of serine proteases on Ig class switching is discussed.
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PMID:Biphasic effect of kallikrein on IgE and IgG1 syntheses by LPS/IL-4-stimulated B cells. 842 28

We investigated the expression of interferon gamma (IFN-gamma)-regulated subunits and the enzymatic activity of proteasomes purified from tumor-derived and normal B lymphocytes representing different stages of B-cell activation/differentiation. The catalytic beta subunits (Lmp2 and Lmp7) and the regulatory subunits (PA28alpha and PA28beta) were expressed at equally high levels in Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs), freshly isolated B-chronic lymphocytic leukemia (B-CLL) cells and normal CD23(-) B lymphocytes. Lmp2 and Lmp7 were selectively down-regulated in germinal center cell-derived Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HD) cell lines. There was a direct correlation between the expression of Lmp2/7 and the chymotrypsin and trypsin-like activities in proteasomes purified from LCLs, BLs and CLL cells, whereas 5 HD cell lines expressing B or T-cell markers exhibited a variable pattern of subunit expression and enzymatic activity. Poor hydrolysis of the fluorogenic substrates by proteasomes from BL cells correlated with a distinct pattern of cleavage of a reference 50mer peptide, production of different sets of degradation products and significantly reduced recovery of a known cytotoxic T-lymphocyte (CTL) target epitope. The enzymatic activity of proteasomes from normal CD23(-) "resting" B lymphocytes resembled that of BL cells in spite of high Lmp2/7 expression. This pattern was not reversed by treatment with the B-cell mitogen, lipopolysaccharide (LPS). The results suggest that different stages of B-cell activation/differentiation are associated with distinct profiles of IFN-gamma-regulated subunit composition and enzymatic activity of the proteasome. This may have important implications for the analysis and manipulation of tumor-specific immune responses.
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PMID:Variations in proteasome subunit composition and enzymatic activity in B-lymphoma lines and normal B cells. 1109 9