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)

The cell-surface glycoproteins CD44 and CD58 are involved in cell adhesion reactions. In this paper 12 monoclonal antibodies in CD44 and two in CD58 are described. Competitive binding assays using CD44 antibodies identified three distinct epitope groups. Antibodies in Group 1 and, with one exception (BRIC 214), antibodies in group 2, but not antibodies in Group 3, recognized epitopes that are sensitive to reduction and to trypsin or chymotrypsin treatment of intact erythrocytes, and so these epitopes probably reside on the N-terminal disulphide-bonded domain of CD44. Antibodies in CD44 did not inhibit the binding of CD58 antibodies to erythrocytes or vice versa. Quantitative binding studies using radioiodinated IgG measured 1888-5592 copies of CD44 and 1772-3290 copies of CD58 on normal erythrocytes. Similar measurements with radioiodinated Fab fragments gave values of 6508-10,450 (CD44) and 3457-7622 (CD58). Immunocytochemical studies indicated that CD44 is much more widely expressed in non-haemopoietic tissues than CD58. Comparison with previously described CD44 antibodies suggests that antibodies in our Group 1 encompass Hermes 2 and that those in Group 2 encompass Hermes 1. All the CD44 antibodies gave weakened reactions with Lu(a-b-) erythrocytes of the In(Lu) type by one or more methods. BRIC 214 and antibodies in epitope Group 3 were used to demonstrate that CD44 on these variant cells gives membrane-bound trypsin and chymotrypsin cleavage fragments of similar molecular weight to those obtained with normal erythrocytes.
 ...
PMID:New monoclonal antibodies in CD44 and CD58: their use to quantify CD44 and CD58 on normal human erythrocytes and to compare the distribution of CD44 and CD58 in human tissues. 172 Oct 39

Salivary immune responses depend on localization of immunocytes in salivary glands. We tested effects of anti-adhesion molecule antibodies and several ligand analogs on in vitro adherence of rat thoracic duct lymphocytes (TDL) to parotid and submandibular gland sections. While TDL adherence to both tissues was markedly decreased by anti-L-selectin mAbs, binding ability after removal of L-selectin by chymotrypsin or PMA suggested that other adhesion systems were involved. Integrin involvement in parotid interactions was indicated by inhibitory effects of anti-HEBF(PP), LFA-1, ICAM-1, and alpha4 integrin antibodies as well as by the PMA-enhanced adherence. Anti-Thy-1 partially inhibited TDL binding to parotid gland, and anti-CD44 partially inhibited submandibular binding. The majority of salivary gland-bound TDL were sIg+ B cells. FACS analysis showed differences in parotid and submandibular endogenous lymphocyte adhesion molecule expression with greater percentages of L-selectin, HEBF(PP), alpha4 integrin, LFA-1, ICAM-1, CD44, and Thy-1-positive cells present in parotid gland. While precise roles of known or novel adhesion molecules in salivary gland lymphocyte retention are not clear, these data suggest that selectins (parotid, submandibular), integrins (parotid), Thy-1 (parotid), and CD-44 (submandibular), as well as other unidentified molecules, are involved.
 ...
PMID:The specificity of adhesive interactions between rat lymphocytes and salivary gland epithelia. 861 87

Myoepithelial cells surround incipient ductal carcinomas of the breast and exert anti-invasive and antiangiogenic effects in vitro through the elaboration of suppressor molecules. This study examines one putative molecule, solubilized CD44 produced by myoepithelial shedding of membrane CD44. Studies with different human myoepithelial cell lines demonstrate that myoepithelial cells express and shed both the 85-kDa standard (CD44s) and the 130-kDa epithelial (CD44v8-10) isoforms, findings further confirmed by the use of isoform-specific antibodies. PMA pretreatment enhances CD44 shedding detected by two different methods at different time points: a reduction in surface CD44 at 2 h by flow cytometry and a marked decrease in both total cellular CD44 and plasma membrane CD44 at 12 h by Western blot. This shedding is both specific for CD44 and specific for myoepithelial cells. This shedding is inhibited by the chymotrypsin inhibitors chymostatin and alpha(1)-antichymotrypsin but not by general metallo-, cysteine, or other serine proteinase inhibitors. Myoepithelial-cell-conditioned medium and affinity-purified solubilized CD44 from this conditioned medium block hyaluronan adhesion and migration of both human carcinoma cell lines and human umbilical vein endothelial cells.
 ...
PMID:Myoepithelial-specific CD44 shedding contributes to the anti-invasive and antiangiogenic phenotype of myoepithelial cells. 1108 85

Our previous studies have demonstrated that myoepithelial cells, which surround incipient carcinomas in situ of the breast and other organs, exert antiinvasive and antiangiogenic effects in vitro through the elaboration of a number of different suppressor molecules among which include the shed membrane CD44. The present study addresses the mechanism of this myoepithelial CD44 shedding. This CD44 shedding is enhanced by PMA pretreatment, is specific for myoepithelial CD44, and inhibited by chymotrypsin-like inhibitors (chymostatin, alpha(1)-antichymotrypsin, TPCK, and SCCA-2) but not by trypsin-like inhibitors (TLCK), nor papain-like inhibitors (SCCA-1) nor hydroxamate-based or general metalloproteinase inhibitors (BB2516 (marimastat), 1,10-phenanthroline, and TIMP-1). The effect of PMA can be mimicked by exogenous chymotrypsin but not by other proteases. The CD44 shedding activity cannot be transferred by conditioned media, cell-cell contact, peripheral membrane, or integral membrane fractions. However, cell-free purified integral plasma membrane fractions obtained from myoepithelial cells pretreated with PMA also exhibit CD44 shedding which is inhibited by chymotrypsin-like inhibitors. These findings support the presence and activation of a putative chymotrypsin-like sheddase as the mechanism of CD44 shedding in myoepithelial cells.
 ...
PMID:Myoepithelial-specific CD44 shedding is mediated by a putative chymotrypsin-like sheddase. 1111 26

CD44 cell surface proteins are involved in leukocyte binding to endothelium and the metastatic spread of tumor cells. Using flow cytometric analysis (FCMA), we investigated the effects of the proteases bromelain, papain, trypsin, and chymotrypsin on the density of CD44 molecules present on human leukemia Molt 4/8 cells. Bromelain was found to be most active in reducing CD44 receptor density. In addition, the effects of the purified bromelain proteinases F4 and F9 were investigated. On Molt 4/8 cells crude bromelain and F9, with the highest proteolytical activity, were found to be most active in reducing CD44 receptor density with a half maximal value of 1.9 mu g/ml and 2.3 mu g/ml, respectively. On human SK-Mel 28 melanoma cells especially F9 showed a strong effect, with a half maximal value of 1.5 mu g/ml. The implications of the findings are discussed with view of the reported antimetastatic activity of orally administrated bromelain with respect to CD44.
 ...
PMID:Bromelain proteinases modulate the cd44 expression on human molt-4/8 leukemia and sk-mel-28 melanoma-cells in-vitro. 2155 2

Bowman-Birk inhibitors (BBIs) are protein molecules containing two inhibitory domains for enzymes similar to trypsin and chymotrypsin. Interest in these inhibitors arose from their properties against the cancer chemically induced by 1,2-dimethylhydrazine (DMH). In this study the effect of two BBI preparations (from Glycine max and Macrotyloma axillare) were evaluated for the prevention of colorectal neoplasia induced by intraperitoneal injections of DMH, given at a dose of 30 mg/kg, during 12 weeks. Mice treated with DMH presented histopathological alterations consistent with tumor development, augmented CD44 expression and increased proteasome peptidase activities. Lysosomal fractions, obtained from the intestines, were chromatographed in a Sepharose-BBI column and increased activity for trypsin and chymotrypsin-like proteases recovered from DMH-treated animals. In parallel, mice treated for eight weeks with BBIs showed a decrease in the chymotrypsin and trypsin-like proteasome activities compared to animals fed on normal diet. For the groups receiving simultaneous treatment with DMH and BBIs, dysplasic lesions were not observed and proteasome peptidase activities were similar to the control group after the 24th week. These results suggest that the mechanism by which BBIs could prevent the appearance of pre neoplastic lesions is associated with inhibition of both the lysosomal and proteasome-dependent proteolytic pathways.
 ...
PMID:Bowman-Birk inhibitors, proteasome peptidase activities and colorectal pre neoplasias induced by 1,2-dimethylhydrazine in Swiss mice. 2232 5

Release of cytokines, growth factors and other life-essential molecules from precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high substrate-specificity. We hypothesized that this is achieved by cleavage-regulatory intracellular-domain (ICD)-modifications of the precursors. We show here that cleavage-stimuli-induced specific ICD-modifications cause structural substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1; epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to chymotrypsin/trypsin or soluble ADAM. This inside-out signal transfer required substrate homodimerization and was prevented by cleavage-inhibitory ICD-mutations. In chimeras, regulation could be conferred to a foreign ectodomain, suggesting a common higher-order structure. We predict that substrate-specific protease-accessibility-regulation controls release of numerous ADAM substrates.
 ...
PMID:Growth factor and co-receptor release by structural regulation of substrate metalloprotease accessibility. 2787 63