Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arg-127 stabilizes the oxyanion of the tetrahedral intermediate formed during Zn2+ carboxypeptidase A-catalyzed hydrolysis. Mutant carboxypeptidases lacking Arg-127 exhibit substantially reduced rates of hydrolysis with the change manifest almost entirely in kcat (kcat/Km is decreased by 10(4) for R127A). Therefore, Arg-127 stabilizes the enzyme-transition state complex but not the ground state enzyme-substrate complex (Phillips, M.A., Fletterick, R., & Rutter, W.J., 1990, J. Biol. Chem. 265, 20692-20698). The addition of guandine, methylguanidine, or ethylguanidine to R127A increases the kcat for hydrolysis of Bz-gly(o)phe by 10(2) without changing the Km. Dissociation constants (Kd) for the guanidine derivatives range from 0.1 to 0.5 M. The binding affinity for the transition state analog Cbz-phe-alaP(o)ala is increased similarly by 10(2); in contrast, the binding affinity of the ground state inhibitor benzylsuccinic acid is not altered. Thus, guanidine derivatives mimic Arg-127 in stabilizing the rate-limiting transition state. Hydrolysis of Bz-gly-(o)phe by wild-type carboxypeptidase, R127K, or R127M is not substantially affected by guanidine derivatives. Additionally, primary amines do not change the activity of R127A. These observations imply that guanidine binds in the cavity vacated by Arg-127 specifically and in a productive conformation for catalysis.
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PMID:Guanidine derivatives restore activity to carboxypeptidase lacking arginine-127. 130 53

(-)3-[125I]iodocyanopindolol (ICYP), a high selective, high specific beta antagonist is employed to characterize beta-adrenoceptors on rat pleural and peritoneal mast cell populations. Results show that non specific binding is low, and that pleural mast cells exhibit greater number of receptors per cell (140,000) than peritoneal cells (90,000). Dissociation constants (Kd) are 0.37 +/- 0.01 and 0.55 +/- 0.02 nM for pleural and peritoneal cells, respectively. Competition experiments show that isoproterenol do not displaces ICYP neither in pleural nor in peritoneal cells. Low concentrations of propranolol displace ICYP from its binding sites, but atenolol does not. Results point to the existence in mast cells of mainly atypical. beta 2-receptors, since the agonist isoproterenol does not compete with the antagonist ICYP.
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PMID:Adrenergic agonists do not compete with the antagonist (-)3-[125I]iodocyanopindolol for binding to rat pleural or peritoneal mast cell adrenergic receptor. 288 71

The preparation of a pure, monoiodinated derivative of mast cell-degranulating peptide (MCD peptide), the mast cell-degranulating peptide from bee venom, has enabled us to identify binding sites in rat brain membranes that have a high affinity and specificity for this peptide. These binding sites are evenly distributed throughout the brain and copurify with synaptic membranes. Saturation-binding curves, determined by rapid centrifugation or filtration assays, indicate a single population of sites with a concentration of 200 fmol/mg membrane protein in partially fractionated, lysed brain membranes. Dissociation constants of 150 and 140 pM were calculated for the iodinated and native peptides, respectively. These binding sites are probably associated with the neurotoxic action of MCD peptide in the central nervous system. No similar binding sites have been identified in peripheral tissue preparations, and other polycationic mast cell-degranulating agents including compound 48/80 show no such specificity. Specific modification of the primary amines, arginine residues, or disulfide bridges of MCD peptide results in a complete loss of binding activity. Other components of bee venom show specificity for the MCD peptide-binding site, suggesting that a class of neurotoxins in bee venom (possibly including secapin and tertiapin, but not apamin) share the specific action of MCD peptide on the central nervous system.
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PMID:The characterization of high-affinity binding sites in rat brain for the mast cell-degranulating peptide from bee venom using the purified monoiodinated peptide. 650 Dec 83

In the present study, we demonstrated that the antiapoptotic function of Bcl-2 in mast cells is significantly dependent on its association with the heat shock protein 90beta (Hsp90beta). Dissociation of these 2 proteins inhibits the antiapoptotic activity of Bcl-2 by initiating the release of cytochrome c from mitochondria into cytosol and increasing the activity of caspase 3 and caspase 7, resulting in mast-cell apoptosis. The antiapoptotic activity of Bcl-2 was greatly affected by knocking-out specifically Hsp90beta using the RNA interference approach. Thus, for the first time, it has been shown that Hsp90beta might modulate the antiapoptotic activity of Bcl-2 at least in mast cells. These findings could have implications for a novel strategy of regulating apoptosis in patients with mastocytosis and other mast cell-associated diseases.
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PMID:Antiapoptotic function of Bcl-2 in mast cells is dependent on its association with heat shock protein 90beta. 1616 81

Alveolar hypoxia (Fi(O(2)) 0.10) rapidly produces inflammation in the microcirculation of skeletal muscle, brain, and mesentery of rats. Dissociation between tissue Po(2) values and inflammation, plus the observation that plasma from hypoxic rats activates mast cells and elicits inflammation in normoxic tissues, suggest that the response to hypoxia is initiated when mast cells are activated by an agent released from a distant site and carried by the circulation. These experiments tested the hypothesis that this agent originates in alveolar macrophages (AM). Male rats were depleted of AM by tracheal instillation of clodronate-containing liposomes. Four days after treatment, AM recovered by bronchoalveolar lavage were <10% of control. Control rats received buffer-containing liposomes. As expected, alveolar hypoxia (Fi(O(2)) 0.10) in control rats increased leukocyte-endothelial adherence, produced degranulation of perivascular mast cells, and increased fluorescent albumin extravasation in the cremaster microcirculation. None of these effects was seen when AM-depleted rats were exposed to hypoxia. Plasma obtained from control rats after 5 min of breathing 10% O(2) elicited inflammation when applied to normoxic cremasters. In contrast, normoxic cremasters did not develop inflammation after application of plasma from hypoxic AM-depleted rats. Supernatant from AM cultured in 10% O(2) produced increased leukocyte-endothelial adherence, vasoconstriction, and albumin extravasation when applied to normoxic cremasters. Normoxic AM supernatant did not produce any of these responses. The effects of hypoxic supernatant were attenuated by pretreatment of the cremaster with the mast cell stabilizer cromolyn. These data support the hypothesis that AM are the source of the agent that initiates hypoxia-induced systemic inflammation by activating mast cells.
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PMID:Alveolar macrophages are necessary for the systemic inflammation of acute alveolar hypoxia. 1765 28

An increase in the intracellular calcium ion concentration ([Ca(2+)]) impacts a diverse range of cell functions, including adhesion, motility, gene expression and proliferation. Elevation of intracellular calcium ion (Ca(2+)) regulates various cellular events after the stimulation of cells. Initial increase in Ca(2+) comes from the endoplasmic reticulum (ER), intracellular storage space. However, the continuous influx of extracellular Ca(2+) is required to maintain the increased level of Ca(2+) inside cells. Store-operated Ca(2+) entry (SOCE) manages this process, and STIM1, a newly discovered molecule, has a unique and essential role in SOCE. STIM1 can sense the exhaustion of Ca(2+) in the ER, and activate the SOC channel in the plasma membrane, leading to the continuous influx of extracellular Ca(2+). STIM1 senses the status of the intracellular Ca(2+) stores via a luminal N-terminal Ca(2+)-binding EF-hand domain. Dissociation of Ca(2+) from this domain induces the clustering of STIM1 to regions of the ER that lie close to the plasma membrane, where it regulates the activity of the store-operated Ca(2+) channels/entry (calcium-release-activated calcium channels/entry). In this review, we summarize the mechanism by which STIM1 regulates SOCE, and also its role in the control of mast cell functions and allergic responses.
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PMID:Ca2+ signaling and STIM1. 2022 8