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)

In the absence of divalent cations M phi lose their spread morphology but remain adherent to tissue culture treated plastic. We have exploited this property of M phi adhesion in vitro, to isolate a rat monoclonal 2F8, which totally inhibits the divalent cation-independent adhesion of M phi to tissue culture treated plastic and is partly responsible for the trypsin-resistant adhesion of M phi to the same substratum. Immunoprecipitation from macrophages and stably transfected Chinese Hamster Ovary Cells revealed that the antigen recognised by monoclonal antibody 2F8 is identical to the murine macrophage scavenger receptor. Macrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidised lipoprotein and the formation of foam cells in atherosclerotic lesions. We have used monoclonal antibody 2F8 to explore the expression of murine macrophage scavenger receptor in lymphoid and non-lymphoid organs of the normal adult mouse and to examine the contribution of macrophage scavenger receptor to macrophage adhesion within tissues.
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PMID:Murine M phi scavenger receptor: adhesion function and expression. 773 92

The factor XII genes of two unrelated factor XII-deficient Japanese families were screened, and two novel mutations were identified. A heterozygous mutation (Q421K) was identified in the gene of a cross-reacting material (CRM)-negative patient with reduced FXII activity (entitled Case 1). No mutations were discovered in the other allele. Case 2 was a CRM-negative patient with severe FXII deficiency. In this case, a homozygous mutation (R123P) was discerned. Expression studies in Chinese Hamster Ovary (CHO) cells demonstrated accumulation of mutant Q421 K factor XII in the cell, and insufficient secretion, while the R123P mutant showed lower levels of accumulation than wild-type, and no evidence of secretion in culture supernatant. In the presence of proteasome inhibitor, all types of FXII (wild-type. Q421K, R123P) accumulated in the cells. Protease protection experiments using the microsomal fraction of these cell lines demonstrated that while 20% wild-type FXII (total wild-type:100%) and 10% R123P mutant (total R123P-type: 40%) were resistant to treatment with trypsin, 50% Q421K-type FXII (total Q421K-type:130%) remained resistant to digestion. From these results, we conclude that Q421K is less susceptible to proteasome degradation than wild-type, but is unable to exit the ER efficiently, resulting in insufficient secretion phenotype. In contrast, R123P is susceptible to proteasome degradation and is not secreted.
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PMID:Identification and characterization of two novel mutations (Q421 K and R123P) in congenital factor XII deficiency. 1177 7

Protease-activated receptor 2 (PAR(2)) is a G protein-coupled cell surface receptor for trypsin-like enzymes. Proteolytic cleavage at a specific site in the extracellular N-terminus exposes a receptor-activating sequence, the 'tethered ligand', which binds intramolecularly to initiate receptor signalling. Peptide or small molecule agonists for PAR(2), devoid of the non-specific and proteolytic effects of enzyme activators, may be promising therapeutic agents for proliferative and inflammatory diseases reportedly mediated by PAR(2). Synthetic hexapeptides that correspond to the native tethered ligand of human or rodent PAR(2) (SLIGKV and SLIGRL, respectively) can activate the receptor independently of proteolytic cleavage; however, known peptide agonists have much lower potency compared to protease-mediated activation. Here, we investigated the agonist activity of 94 hepta and octapeptide derivatives of the human and rodent PAR(2)-tethered ligand sequences in human airway epithelial (A549) cells which endogenously express PAR(2). Thirty synthetic peptides were found to be as potent as or more potent than SLIGRL on the basis of intracellular Ca(2+) responses. The more active peptide agonists were also examined for agonist cross-reactivity at PAR(1) in Chinese Hamster Ovary (CHO) cells that endogenously express functional PAR(1) but not PAR(2). Two potent and PAR(2)-selective agonists were further examined for their capacity to relax phenylephrine-contracted rat aortic rings. Our findings reveal an important role for carboxyl extensions to native PAR(2) activating peptides in potentiating agonist activity.
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PMID:Hepta and octapeptide agonists of protease-activated receptor 2. 1789 Jun 55