Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The generation of superoxide anion and release of granule contents are essential to the bactericidal function of neutrophils, but may also contribute to host tissue damage during inflammation. In previous studies (J. Immunol. 146:2388), we have demonstrated that the acute phase reactant alpha-1-antichymotrypsin (ACT), a potent inhibitor of the serine protease cathepsin G, also suppresses superoxide anion generation. The inhibitory effect of ACT was not directly linked to its antiproteolytic activity and may reflect interaction at a site other than its reactive loop. To further characterize the mechanism of inhibition, we investigated the direct effects of ACT on the NADPH oxidase enzyme complex and the signaling pathways that regulate motivation of the respiratory burst. We present evidence that ACT does not intefer with agonist-stimulated calcium mobilization or translocation and activity of protein kinase C. ACT was an effective inhibitor of superoxide anion generation in membrane preparations isolated from PMA-activated cells. These results support the notion that ACT is acting on a component of the active assembled NADPH oxidase complex. Thus, ACT may have an important role in regulation of specific aspects of the inflammatory processes and the modulation of toxic oxygen-based host tissue damage.
 ...
PMID:Alpha-1-antichymotrypsin inhibits the NADPH oxidase-enzyme complex in phorbol ester-stimulated neutrophil membranes. 132 90

Accumulating evidence has demonstrated that protein kinase C (PKC) and protease nexin-1 (PN-1) may be involved in neuronal differentiation including migration, neurite outgrowth, target recognition, and synaptogenesis. We investigated the potential roles of PKC and PN-1 in neurite outgrowth of human neuroblastoma cell line, GOTO. Upon withdrawal of serum GOTO cells extended neurite processes within 3 h and formed fine network of neurites after 24 h. This morphological change was completely inhibited by thrombin and phorbol-12-myristate-13-acetate (PMA). Withdrawal of serum increased the neurofilament (NF)-L and -M mRNA levels and thrombin did not inhibit the effect of withdrawal of serum. A potent PKC inhibitor, H-7 induced neurite outgrowth in the presence of serum, however, it did not increase the NF mRNA levels. Actinomycin D and cycloheximide did not inhibit the initial neurite outgrowth induced by withdrawal of serum, while these inhibited the increase in the NF mRNA levels. Thrombin retracted the serum depletion-induced neurites but did not retract the neurites induced by H-7. The specific activity and subcellular localization of PKC did not differ between GOTO cells cultured in serum-containing and -free media for 12 h. The serine protease inhibitory activity was undetectable in the serum-free conditioned medium of GOTO cells but the PN-1 mRNA was clearly detected by Northern blot analysis to a less extent than glial cells. Withdrawal of serum or treatment with H-7 did not increase the PN-1 mRNA level in GOTO cells, but thrombin increased its level about 7 folds in serum-free condition. These results indicate that the initial neurite outgrowth requires neither new RNA nor protein synthesis, and that PKC negatively regulates neurite outgrowth and thrombin blocks neurite outgrowth through PKC-dependent pathways.
 ...
PMID:Regulation of neurite outgrowth through protein kinase C and protease nexin-1 in neuroblastoma cell. 145 85

The inhibitory effect of a serine protease-inhibiting tetra-benzamidine derivative, TAPP-Br, on the cell growth of 8 human colon carcinoma cell lines was examined and the mechanism of the inhibition was analyzed. TAPP-Br inhibited the cell growth of all the colon carcinoma cell lines, and this effect was irreversible. The expression of mRNAs for nuclear oncogenes such as MYC, FOS and JUN was decreased by TAPP-Br after treatment for 3 h and the effect continued for 48 h. mRNA expression of epidermal growth factor receptor, transforming growth factor-beta and type IV collagenase was suppressed at 48 h after the initiation of TAPP-Br treatment, suggesting an indirect action of TAPP-Br. TAPP-Br decreased protein kinase C activity in the particulate fraction, whereas it increased the enzyme activity in the soluble fraction. These findings overall suggest that the serine protease inhibitor, TAPP-Br, might inhibit the cell growth of colon carcinoma cell lines through suppressing the expression of genes whose promoter contains a 12-O-tetradecanoylphorbol-13-acetate-responsive element or serum-responsive element.
 ...
PMID:A serine protease-inhibitory benzamidine derivative inhibits the growth of human colon carcinoma cells. 151 49

The chicken urokinase-type plasminogen activator (uPA) cDNA and gene have been isolated and the complete nucleotide sequence of each established. cDNA sequence and Northern blot RNA analysis indicate that the chicken uPA mRNA is approximately 2500 nucleotides in size and contains a large 3'-noncoding region (998 nucleotides). The predicted amino acid sequence of the chicken uPA primary translation product (434 residues) suggests a domain architecture comparable to the mammalian uPA proteins with the form: (i) signal peptide, (ii) growth factor domain (GF), (iii) kringle domain (K), and (iv) serine protease domain (C). The overall sequence identity between the chicken and human proteins is 43.1%, with 56.3, 48.5, and 45.6% identity in the GF, K, and C domains, respectively. The chicken uPA gene is similar to the mammalian uPA genes in both size (8158 base pairs between transcription initiation and polyadenylation sites) and organization (11 exons). However, the sequence of the chicken uPA gene is similar to the mammalian uPA genes only within the protein-coding portions of exons. The transcription initiation site is flanked by a remarkably G/C-rich region (77% between nucleotides -1 and -300) which contains a TATA element and several potential transcription factor Spl-binding sites. The promoter region also contains several repeat elements, including two 11-nucleotide repeats that encompass six potential transcription factor AP-2-binding sites. This work provides a foundation for exploring the mechanism(s) by which protein-tyrosine kinase pp60v-src and protein kinase C modulate uPA gene transcription.
 ...
PMID:The chicken urokinase-type plasminogen activator gene. 229 32

Superoxide anion production by polymorphonuclear leukocytes stimulated with phorbol 12-myristate 13-acetate is known to be inhibited by a number of inhibitors and substrates of serine proteases, in particular by tosylphenylalanylchloromethane (TosPheCH2Cl) and to a lesser extent by tosyllysylchloromethane (TosLysCH2Cl). We have reinvestigated the characteristics of this inhibition, in view of the fact that other serine protease inhibitors with similar specificities, phenylmethanesulfonyl fluoride and leupeptin, were without effect. We found that the inhibition of phorbol-ester-induced superoxide production after cell preincubation with the chloromethanes followed saturation kinetics, with Kinact and kinact values of 100 microM and 31 min-1 for TosPheCH2Cl and 2 mM and 18 min-1 for TosLysCh2Cl. We also showed that the two compounds, which can inhibit protein kinase C in vitro, inhibited neither its activity in vivo, nor its translocation induced by phorbol myristate acetate. Furthermore the intracellular non-protein sulfhydryl group content was not affected by the treatment with the chloromethanes. Finally, addition of the inhibitors to stimulated cells also led to a time-dependent, concentration-dependent inhibition of superoxide production. Altogether, our results suggest that the chloromethane target is neither a protease nor protein kinase C and is not involved in NADPH oxidase activation, but rather in maintenance of its activity. The possible identity of this protein is discussed.
 ...
PMID:Inhibition of NADPH oxidase by aminoacyl chloromethane protease inhibitors in phorbol-ester-stimulated human neutrophils: a reinvestigation. Are proteases really involved in the activation process? 254 67

Recent studies have demonstrated that a calcium-sensitive protease converts Ca2+/phospholipid-dependent protein kinase C to a Ca2+/phospholipid-independent form during the activation of human neutrophils. In this paper, the results of the purification and characterization of a calcium-dependent cytosolic protease from neutrophils is reported. Calcium-dependent protease has been purified 1062-fold from human neutrophils and behaves as a single species on native polyacrylamide gels. The protease is active in the neutral pH range with no observable activity amide gels. The protease is active in the neutral pH range with no observable activity at pH values greater than 8.0, has an absolute requirement for calcium for expression of activity with half-maximal activity observed at 12 microM free calcium, and has an apparent molecular weight of 110,000 based on gel filtration. The protease requires the presence of dithiothreitol for activity and is inhibited by sulfhydryl inhibitors, leupeptin, and antipain but not by serine protease inhibitors, pepstatin, or orthophenanthroline. The protease is also susceptible to inactivation by autoproteolysis. Based on the similarities of this calcium-dependent protease with calpains from a variety of other mammalian tissues, the protease isolated from human neutrophils appears to be a calpain I.
 ...
PMID:Purification and characterization of calpain from human polymorphonuclear leukocytes. 283 20

Biochemical events involved in both IgE-dependent and IgE-independent mediator release from basophils and mast cells were analyzed. The results revealed that bridging of IgE receptors activates a variety of membrane-associated enzymes, such as serine protease, phospholipase C, methyltransferases and adenylate cyclase, resulting in the stimulation of phosphatidylinositol (PI) turnover and a transient increase in both phospholipid methylation and intracellular cAMP. Mobilization of intracellular Ca2+ monitored by Quin-2 fluorescence is detected within 5 s after antigen challenge and appears to be the earliest intracellular change detectable after receptor bridging. Stimulation of PI turnover results in the generation of inositol 1,4,5-triphosphate (IP3) and of 1,2-diacylglycerol (DAG), which in turn activates protein kinase C. Evidence was obtained that the guanyl nucleotide (GTP)-binding protein Ni is not involved in the transduction of IgE-mediated triggering signals for mediator release. Although the sequence of enzyme activation following receptor bridging is not clear, the results suggest that the mobilization of intracellular Ca2+ is a crucial initial signal in the IgE-mediated activation of basophils and mast cells. In the mediator release induced by IgE-independent stimuli, enzymes involved in the mediator release are different from one stimulus to another. The results indicate the presence of multiple biochemical pathways for mediator release from basophils and mast cells.
 ...
PMID:Activation of basophils and mast cells for mediator release. 310 38

The effects of insulin, the tumour promotor tetradecanoyl phorbol acetate (TPA), TSH and combinations of these factors on growth and DNA synthesis have been examined in the FRTL-5 cell strain and in sheep thyroid cells. In addition the regulation of the production by sheep thyroid cells of the insulin-like growth factors (IGF) by TSH and their possible autocrine roles have been investigated. We found that insulin and the IGF's stimulated DNA synthesis in both rat FRTL-5 cells and sheep cells. TPA also stimulated growth in both cell types, and its effects were additive to those of insulin. In the FRTL-5 cells, TPA was a less potent stimulator of growth than TSH, but the effects of TPA and TSH were not additive which may imply growth stimulation through a common pathway. In sheep cells TSH was not mitogenic and did not appear to activate protein kinase C, the receptor for TPA. Sheep cells, unlike FRTL-5 cells, were found to produce IGF-I and IGF-II, and their syntheses were regulated by TSH. Sheep cells were also found to produce IGF-binding proteins which may modulate the biologic effects of the IGF's. Sheep thyroid IGF binding proteins were found to copurify with urokinase-like plasminogen activator on immunoaffinity chromatography. The production of this serine protease has also been shown to be regulated by TSH.
 ...
PMID:Role of non-TSH factors in thyroid cell growth. 347 6

Prostate-specific antigen (PSA) is a 33 kD protein synthesized in the epithelial cells of the prostate gland. It is a serine protease that belongs to the subgroup of kallikreins, among which it is very similar to a putative enzyme called human glandular kallikrein (hGK-1). Although the hGK-1 enzyme remains to be characterized in vivo, the hGK-1 gene is expressed in the same prostatic epithelial cells as the PSA gene. Expression of the PSA gene is under complex control and the steady-state level of PSA mRNA is increased by androgens, and decreased by epidermal growth factor and activation of protein kinase C. This suggests the existence of several regulatory elements within the cis-acting control elements of the PSA gene. As a seminal serine protease, PSA has been shown to digest the high molecular weight seminal vesicle protein, seminogelin. However, it is likely that this does not constitute the only natural substrate of PSA, as PSA has been shown to degrade insulin-like growth factor-binding protein-3. Serum PSA concentrations are frequently increased in patients with prostatic cancer, but this is also the case in patients with benign prostatic hyperplasia. Thus, PSA measurements alone are not useful as a screening tool for undiagnosed prostatic cancer. However, serum PSA concentrations can be successfully used together with other methods in diagnosing prostatic diseases and in monitoring the successfulness of treatments for prostatic cancer.
 ...
PMID:Prostate-specific antigen and human glandular kallikrein: two kallikreins of the human prostate. 752 Nov 73

A widely accepted model for the association of extrinsically bound proteins with acidic lipid-containing membranes has been that approach of the protein to the membrane induces a domain of acidic lipids that serves as the protein binding site. This model has been applied to a variety of membrane proteins including those that participate in the proteolytic complex that converts prothrombin to thrombin during the final stages of the blood coagulation cascade. The 'prothrombinase complex' consists of a serine protease (factor Xa), its protein co-factor (factor Va) and the substrate itself (prothrombin), all bound to phosphatidylserine (PS)-containing membranes derived from stimulated platelets. We have used three approaches to test the domain model as it applies to the proteins of this complex. First, phase diagrams describing the mixing of acidic and neutral lipids have failed to provide evidence for extensive acidic lipid domains (on the order of 50 or more lipid molecules) induced by protein biding. Second, pyrene-containing neutral and acidic phospholipids have been used to test for the occurrence of domains of as few as 20-30 lipids associated with binding of the membrane-binding fragment 1 region of prothrombin. Again, no evidence for domains was obtained. Finally, we have shown that binding of these proteins can be described in terms of a generalized model that presumes an acidic-lipid-independent surface adsorption combined with specific binding of acidic lipids to 'm' sites on a protein. Our results suggest that the concept of a protein-induced domain should not be applied indistriminately to explain binding of extrinsic membrane proteins such as the protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Are acidic lipid domains induced by extrinsic protein binding to membranes? 776 85


1 2 3 4 5 6 Next >>