UNIPROT:P15088 - FACTA Search

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Query: UNIPROT:P15088 (mast cell)
14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both 13C NMR and electronic absorption spectral studies on cobalt(II) carboxypeptidase A in the presence of acetate and phenylacetate provide evidence for two binding sites for each of these agents. The transverse relaxation rate T2-1 for the 13C-enriched carboxyl groups of the inhibitors is significantly increased when bound to the paramagnetic cobalt carboxypeptidase as compared to the diamagnetic zinc enzyme. The acetate concentration dependence of T2p-1 shows two inflections indicative of sequential binding of two inhibitor molecules. The cobalt-13C distances, calculated by means of the Solomon equation, indicate that the second acetate molecule binds directly to the metal ion while the first acetate molecule binds to a protein group at a distance 0.5-0.8 nm for the metal ion, consistent with it binding to one or more of the arginyl residues (Arg-145, Arg-127, or Arg-71). In the case of phenylacetate, perturbation of the cobalt electronic absorption spectrum shows that binding occurs stepwise. 13C NMR distance measurements indicate that one of the two phenylacetates is bound to the metal in the EI2 complex. These binding sites may correspond to those identified previously by kinetic means (one of which is competitive, the other noncompetitive) with peptide binding. The studies further indicate that it should be possible to map the protein interactions of the carbonyl groups of both substrate and noncompetitive inhibitors during catalysis by means of 13C NMR studies with suitably labeled substrates and inhibitors.
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PMID:13C NMR studies of carboxylate inhibitor binding to cobalt(II) carboxypeptidase A. 334 59

The murine mast cell line PB-3c is dependent on interleukin 3 (IL-3) with respect to survival and proliferation. These cells also require IL-3 to display antigen-mediated serotonin release, which is coupled to a transient increase of cytosolic free calcium ([Ca2+]i). The antigen-mediated exocytosis is inhibited by phorbol 12-tetradecanoate 13-acetate (PTA), an activator of phospholipid/Ca2+-sensitive protein kinase. In contrast, the malignant mast cell variant PB-1 is IL-3 independent with respect to proliferation but is unable to undergo antigen-mediated exocytosis. Yet this cell line exhibits basal levels of [Ca2+]i, serotonin content, and numbers of IgE receptors comparable to those of PB-3c cells. Subcellular distribution studies revealed that the specific activity of cytosolic protein kinase C of PB-1 cells was only 40% of that found in PB-3c cells. Furthermore, the PB-1 cells showed a significantly higher specific activity of membrane-bound protein kinase C than PB-3c cells. Scatchard plot analysis of [3H]-phorbol 12,13-dibutyrate binding to intact PB-1 cells demonstrated the presence of 20% high-affinity (Kd = 6 nM) and 80% low-affinity (Kd = 60 nM) phorbol ester receptors, whereas PB-3c cells displayed only the low-affinity phorbol ester binding. Immunological characterization of protein kinase C from both cell lines revealed the presence of a normal 77-kDa protein kinase C holoenzyme in both cell lines. In addition, a 72-kDa protein kinase C-related protein band was found mainly in the membrane fraction of the PB-1 variant. It is suggested that this altered and membrane-bound form of protein kinase C may be involved in the blockage of the antigen-mediated exocytosis of PB-1 cells.
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PMID:Altered protein kinase C in a mast cell variant defective in exocytosis. 349 90

A series of 70 patients with the squamous cell carcinoma of the lip and followed-up for at least 5 years, was assessed on light microscopy and using histochemical staining for ANAE (acid-naphthyl acetate esterase) to demonstrate the morphological manifestations of tumor-host reactivity. The factors analysed include cancer differentiation (intrinsic malignancy) and stromal reactions (intensity of the immunocompetent cell infiltrate including the mast cells and the subpopulations, i.e. B- or T lymphocytes or mononuclear phagocytes). Differentiation of the lip cancer was shown to be directly (although not statistically significantly) related to the 5-year survival, as was also the intensity of the stromal immunocompetent cell infiltration. Cancer metastases were evidently the most powerful prognostic determinants, their development being influenced both by the intensity of the stromal immunocompetent cell infiltrate and cancer differentiation. B lymphocytes far outnumbered the T and MPS cells in all the infiltrates studied, the percentages of the latter two cell types, however, being inversely related to the intensity of the infiltrate. The cell composition in the infiltrates was seemingly without effect on the frequency of metastases and the 5-year survival, as was the stromal mast cell reaction, too. It was concluded that analysis of tumor-host relationships using a variety of morphological and immunohistochemical techniques may be of benefit in predicting the clinical course of lip cancer.
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PMID:Tumor differentiation and tumor-host interactions as prognostic determinants in squamous cell carcinoma of the lip. 351 41

Mouse bone marrow-derived mast cells passively sensitized with monoclonal IgE released paf-acether (platelet-activating factor) and beta-hexosaminidase when challenged with the specific antigen. The formation and the release of paf-acether followed an early increase in the activity of the acetyltransferase, the main enzyme in paf-acether biosynthesis. The antigen-induced activation of the acetyltransferase was dependent on physiologic temperature and on the presence of Ca2+. By using microsomal fractions from unchallenged and challenged mast cells, the Vmax values were 3.5 and 12.0 nmol/min/mg of protein, respectively, whereas in both cases a Km value for acetyl-coenzyme A of 172 microM was measured. The stimulation of acetyltransferase could be mimicked in vitro under experimental conditions which favor phosphorylation, i.e. adding ATP and Mg2+ to lysates from unchallenged mast cells. In contrast, ATP and Mg2+ were uneffective on lysates from challenged cells that exhibited high level of acetyltransferase activity, suggesting that phosphorylation of the enzyme already took place at the time of cell stimulation. Moreover, addition of alkaline phosphatase to microsomal fraction obtained from either antigen-challenged mouse bone marrow-derived mast cells or unchallenged cells, resulted in 52% and 43% loss of acetyltransferase activity, respectively. Phorbol myristate acetate treatment of cells doubled the enzyme activity supporting the phosphorylation hypothesis. Thus, we report on the immunologic activation of a key enzyme for paf-acether synthesis and on the mechanism of this activation in a pure mast cell population. A link between bridging of IgE receptors and the activation of an enzyme critical to the formation of a lipid mediator is thereby evidenced.
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PMID:Biosynthesis of paf-acether. IX. Role for a phosphorylation-dependent activation of acetyltransferase in antigen-stimulated mouse mast cells. 358 83

An intimate interplay between the host factors and the tumour seems to be operative in lip cancer, and is undoubtedly capable of modifying the clinical course of the disease. A series of 70 patients with squamous cell carcinoma of the lip was assessed by light microscopy and using histochemical staining for acid alpha-naphthyl acetate esterase to demonstrate the morphological manifestations of tumour-host reactivity. The factors analysed include stromal reactions; intensity of the immunocompetent cell infiltrate including mast cells, and the subpopulations, i.e. B or T lymphocytes and mononuclear phagocytes (MPS cells). B lymphocytes far outnumbered the T and MPS cells in all the infiltrates studied, the percentages of the latter two cell types being inversely related to the intensity of the infiltrate, however. The cell composition in the infiltrates lacked statistically demonstrable effect on the frequency of metastases and the 5-year survival, as did the stromal mast cell reaction, too.
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PMID:Immunocompetent cell reaction in prognostic evaluation of squamous cell carcinoma of the lip. 361 94

Rapid-scanning cryospectroscopy of cobalt(II)-substituted carboxypeptidase A serves to identify and characterize ternary enzyme-substrate-inhibitor (IES) complexes formed by the interaction between the enzyme, a peptide substrate, and a noncompetitive inhibitor. A cobalt absorption spectrum distinct from any induced by peptide or inhibitor alone signals formation of the IES complex. Tight-binding noncompetitive inhibitors containing an aromatic ring, e.g., beta-phenylpropionate, cause the IES complex to form much more slowly than simple binary complexes of the enzyme with either peptide or inhibitor. An inhibitor such as acetate, which binds more weakly and is less bulky, permits the IES complex to form relatively quickly. Remarkably, the cobalt spectra of the IES complexes match those previously found for the steady-state ester (depsipeptide) intermediates. Chemical quenching studies have demonstrated that in these ester intermediates the scissile bond is broken [Galdes, A., Auld, D. S., & Vallee, B. L. (1986) Biochemistry 25, 646-651]. This finding, in conjunction with the present studies, implies that a peptide and a noncompetitive inhibitor of its hydrolysis occupy the same binding loci as the hydrolytic products of a depsipeptide and further indicates that breakdown of an enzyme-biproduct complex is rate-determining for the turnover of depsipeptides.
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PMID:Rapid-scanning cryospectroscopy of enzyme-substrate-inhibitor complexes of cobalt carboxypeptidase A. 376 37

Rats primed by infection with the intestinal nematode Nippostrongylus brasiliensis and challenged intravenously with soluble whole-worm antigen undergo systemic anaphylactic shock. The primary lesions are in the gut and include increased permeability of the mucosa together with release, into enteric secretions, of a mucosal mast cell (MMC)-specific serine proteinase, rat mast cell protease II (RMCP-II). This enzyme is also released into the blood of shocked rats. These manifestations of anaphylaxis were abolished in rats previously treated with corticosteroids (methylprednisolone acetate, 25 mg per kg of body weight, 48 and 24 hr before i.v. challenge with antigen). Suppression of the response was associated with depletion of RMCP-II and of MMC from the intestinal mucosa. Depletion occurred 4-24 hr after treatment with as little as 1 mg of methylprednisolone per kg. By contrast, neither connective tissue mast cells nor serum levels of parasite-specific IgE were depleted in rats given 2 X 25 mg of methylprednisolone per kg. The capacity of unprimed treated rats to mount passive cutaneous anaphylaxis was, however, impaired.
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PMID:Depletion of mucosal mast cell protease by corticosteroids: effect on intestinal anaphylaxis in the rat. 388 54

The stability constants of the 1:1 complexes between Cu2+ and Zn2+ with formate, acetate and several phenylalkanecarboxylates, i.e. C6H5-(CH2)n-COO- with n = 0 to 5, are summarized for water, 50% aqueous ethanol and 50% aqueous dioxane (I = 0.1 M; 25 degrees C): Complex stability depends upon carboxylate group basicity. The influence of varying amounts of ethanol or dioxane (up to 90%) on the stability of the Cu2+ and Zn2+ (M2+) complexes with formate and acetate (CA) was measured by potentiometric pH titrations. The values for pKHH(CA) and log KMM(CA) increase, as expected, with increasing amounts of the organic solvents, i.e. with decreasing solvent polarity. The changes in the equilibrium constants are also evaluated with regard to the mole fractions of the organic solvents and the corresponding dielectric constants. These results may be used to estimate for low dielectric cavities in proteins the equivalent solution dielectric constant on the basis of enhanced carboxylate basicity or metal ion binding capability (method 1). Furthermore, the measured stability constants are used for comparisons of the coordination tendency of carboxylate ligands towards zinc(II)-metalloenzymes (method 2); in this way the equivalent solution dielectric constants in the active-site cavities of bovine carbonic anhydrase and carboxypeptidase A are estimated: the values are of the order of 35 and 70, respectively. This method seems to be generally applicable to metalloproteins.
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PMID:An estimation of the equivalent solution dielectric constant in the active-site cavity of metalloenzymes. Dependence of carboxylate-metal-ion complex stabilities on the polarity of mixed aqueous/organic solvents. 393 Feb 43

The epidermal and dermal effects of protracted 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment (2 micrograms TPA twice weekly) of Sencar mouse skin were studied using cell kinetics and morphometric techniques. In addition, regression of TPA-induced changes was evaluated after cessation of 56 topical applications. During the first week of treatment a reactional hyperplasia, characterized by cell damage, edema, and acute inflammation in both epidermis and dermis, occurred. This picture changed gradually during the following 3 weeks: an epidermal hyperplasia devoid of involutional or inflammatory features was accompanied by a moderate to mild chronic inflammation of the dermis and a hyperplasia of the hair follicles. This remained throughout the experimental period until the topical TPA treatment ceased. Although TPA induced papillomas in only 5% of the animals (maximum = 2 papillomas/animal and no carcinomas), all sustained marked epidermal hyperplasia of approximately 4 to 5 times the normal thickness, and increased the number and volume of hair follicles. The [3H]thymidine pulse-labeling index of the basal layer was approximately 32% (normal congruent to 6%). The level of dark keratinocytes remained constant; i.e., 8% of the basal cells were identified as dark cells during the entire experiment. At the subepidermal level the dermal thickness and total cellularity increased, although the proportion of the different cell types changed during the treatment. The mast cell population increased remarkably. After TPA treatment ceased, most of these parameters regressed abruptly during the first 2 weeks. Two to 4 months later, the epidermis was slightly thinner, and the labeling index was 50% lower than normal (2.8%). This study shows that prolonged repetitive TPA applications induced a steady-state hyperplasia without tachyphylaxis, and that this alteration regressed rapidly after treatment ceased. In addition, labeling-index values lower than normal were reached soon after normalization, suggesting that a possible selection of keratinocytes, dependent on TPA for proliferation, took place during the chronic administration of topical TPA. The number of hair follicle, capillary vessels, mast cells, and the dermal thickness never reached normal values after treatment. These important changes in the dermis and hair follicles indicate that the target cells for tumor promoters are not confined to the epidermis alone, and that these tissues could participate actively in carcinogenesis directly, either as tumor-originating tissues (hair follicles), or as inducers or helpers of neoplastic growth (connective tissue cells).
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PMID:Cutaneous changes during prolonged application of 12-O-tetradecanoylphorbol-13-acetate on mouse skin and residual effects after cessation of treatment. 398 7

The degree of metachromasia of mast cell granules is known to vary with the type of tissue fixation and among different tissues and species. The present study sought to determine whether mast cells in dog skin are heterogeneous with respect to fixation and staining properties. We performed skin biopsies in six anesthetized, atopic dogs and one mongrel dog. One biopsy was fixed in formalin and a second, from a parallel abdominal site, was fixed in basic lead acetate (Mota's solution). Adjacent sections from each biopsy were stained with alcian blue (1%, pH 0.5) or for chloroacetate esterase activity. In alcian blue-stained sections, one-third fewer mast cells were detected in skin fixed in formalin (1,836 +/- 454 mast cells/mm3, mean +/- SEM) than in skin fixed in basic lead acetate (2,684 +/- 527 mast cells/mm3) (P less than 0.05). The chloroacetate esterase reaction detected the larger number of mast cells regardless of the fixative used. We conclude that mast cell heterogeneity, as demonstrated by metachromatic staining following different types of tissue fixation, exists in dog skin. "Typical" mast cells stain with alcian blue regardless of fixation; however, "atypical" mast cells exhibit metachromasia only after fixation in basic lead acetate. Both the typical and atypical types of mast cells have chloroacetate esterase activity.
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PMID:Mast cell heterogeneity in dog skin. 408 28

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