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)

Comparison of various chloroplast-type ferredoxin sequences, chemical and enzymic modifications, reconstitution experiments, and fluorescence measurement of chloroplast-type ferredoxins have led to the following conclusions. 1. Tyrosine, histidine, and tryptophan residues are not directly involved in the oxidation-reduction mechanism of ferredoxins. The four indispensible cysteine residues in spinach ferredoxin which constitutes a part of the iron-sulfur cluster are located at residues 39, 44. 47 and 77. Two out of six cysteine residues in Spirulina ferredoxin could be easily modified with vinylpyridine without the loss of reconstitutive ability i.e. the apoferredoxin could be converted to the holoform by the addition of iron and sulfide. 2. Spinach ferredoxin was digested with carboxypeptidase A and the terminal alanine could be removed without loss of the spectral properties of native ferredoxin. However, the removal of the terminal three residues gave rise to the loss of reconstitutive ability. 3. The amino groups of spinach ferredoxin were modified by acetic anhydride and four residues were acetylated. The acetylated preparation of ferredoxin had an unique spectrum. Upon the addition of high concentration of ions the spectrum of this derivative resembled the spectrum of native ferredoxin. Acetylferredoxin did not combine with ferredoxin-NADP reductase, but upon the addition of moderate concentrations of cations, it did bind to this enzyme.
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PMID:Structure and function of chloroplast-type ferredoxins. 78 73

Methylene hydroxylation by cytochrome P-450(cam) (cytochrome m) can be resolved into four distinct steps: substrate addition, m(o) --> m(os); reduction, m(os) --> m(rs); dioxygen addition, m(rs) --> m(O2) (rs); followed by a second putidaredoxin (Pseudomonas putida ferredoxin)-mediated reduction and product formation. The isolated ferrous oxy-substrate complex exhibits first-order decay kinetics with the relatively slow rate constant of k [unk] 0.01 sec(-1), at 25 degrees , without product release. Putidaredoxin addition accelerates the decomposition with second-order kinetics, k [unk] 51,000 M(-1) sec(-1), and initiation of product formation. Cytochrome m forms a complex with putidaredoxin with dissociation constant of K(D) = 3 muM. In the complete three-protein hydroxylase system, consisting of cytochrome m, putidaredoxin, and the reductase (a DPNH-specific flavo-protein), camphor hydroxylation occurs with a stoichiometry of 1 mole each of DPNH and O(2) used per mole of product formed; the K(M) for putidaredoxin is about 4.2 muM.Putidaredoxin, on treatment with carboxypeptidase A, loses one molecule each of tryptophan and glutamine sequentially from the carboxy terminus to expose a terminal arginine. The tryptophan-free product has been separated from native putidaredoxin and other impurities, and retains the visible and electron paramagnetic resonance spectra and the redox potential of the active center of native putidaredoxin. This modified redoxin binds less tightly to cytochrome m, K(D) [unk] 150 muM, and is 50 times less effective in stimulation of the m(O2) (rs) decay rate. A similar decrease in specific activity is observed in the complete hydroxylase system.
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PMID:A role of the putidaredoxin COOH-terminus in P-450cam (cytochrome m) hydroxylations. 453 Feb 69

The ferredoxin (Fd) molecule is a small non-mammalian immunogenic protein containing 55 amino acid residues with only two major antigenic determinants located with the NH2-terminal heptapeptide and the COOH-terminal pentapeptide. Selective enzyme cleavages of Fd with either trypsin or carboxypeptidase A result in the inactivation of the antigenic determinants by the removal of a tripeptide at the NH2-terminal and two amino acid residues at the COOH-terminal, effectively leaving 52 and 53 amino acid fragments respectively, each containing a single antigenic determinant. Fd digested with both enzymes yielded a 50 amino acid peptide with both determinants inactivated. Purity of these digests was assessed using monoclonal antibodies in standard and antigen-blocking ELISAs. The doubly digested peptide had virtually no reactivity with anti-Fd sera, reconfirming that the central cysteine-rich region is serologically silent. It was found that the sum of the reactivities of the N- and C-determinant-bearing peptides as equal to that of the native Fd and that the ratio of the reactivities could be used to assess determinant selectivity in the response to Fd in congenic recombinant strains of mice. This method was used in mapping the determinant selectivity in the antibody response to the MHC of mice to the left of the I-B subregion. Use of the B10.HTT strain indicated that separate genes mapping to the same subregion code for the magnitude of the antibody response and the determinant selectivity of the response.
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PMID:The use of unideterminant fragments of ferredoxin in the genetic mapping of determinant specificity of the immune response. 618 Mar 12

One of the primary responses observed following antigen-induced cross-linking in mast cells is an increase in the phosphorylation of certain cellular proteins on tyrosine residues. Stimulation of protein-tyrosine kinase activity appears to be necessary for induction of downstream responses such as degranulation. The role of nonreceptor protein-tyrosine kinases in the signal transduction pathway initiated by Fc epsilon RI engagement in an interleukin-3-dependent mast cell line has been examined. The results presented here show that the enzymatic activity of Lyn is increased within seconds of receptor engagement. Syk activity also undergoes a rapid and transient increase, reaching a peak at approximately 30 s. Similarly, the activity of Fer, representing a third class of nontransmembrane protein-tyrosine kinase increases as well, with its activity peak reached at 1 min poststimulation. The enzymatic activities of Syk and Fer were found to correspond to anti-phosphotyrosine antibody reactivity. Phosphorylation of tyrosine residues of the beta and gamma chains of Fc epsilon RI increased concomitant with increased protein-tyrosine kinase activity. These results indicate that at least three classes of nontransmembrane protein-tyrosine kinases are involved in mast cell FceRI signaling and that the activation of these classes of enzymes is temporally regulated.
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PMID:Temporal activation of nontransmembrane protein-tyrosine kinases following mast cell Fc epsilon RI engagement. 755 93

Mast cells play important roles in inflammation and immunity and express the high-affinity immunoglobulin E receptor (Fc epsilon RI) and the receptor protein-tyrosine kinase Kit. Aggregation of Fc epsilon RI via antigen binding elicits signals leading to the release of preformed inflammatory mediators as well as de novo-synthesized lipid mediators and cytokines and to elevated cell adhesion and migration. Here, we report that in mouse bone marrow-derived mast cells, Fer kinase is activated downstream of activated Fc epsilon RI and activated Kit receptor, and this activation is abolished in cells homozygous for a kinase-inactivating mutation in Fer (fer(DR/DR)). Interestingly, the highly related Fps/Fes kinase is also activated upon Fc epsilon RI aggregation. This report represents the first description of a common signaling pathway activating Fer and Fps/Fes. While Fer-deficient cells showed similar activation of the Erk mitogen-activated protein (MAP) kinases, p38 MAP kinase activation was less sustained than that in wild-type cells. Although no major defects were observed in degranulation, leukotriene biosynthesis, and cytokine secretion, Fer-deficient cells displayed increased adhesion and decreased motility upon activation of Fc epsilon RI and the Kit receptor. The restoration of Fer kinase activity in fer(DR/DR) mast cells resulted in prolonged p38 kinase activation and increased antigen-mediated cell migration of sensitized mast cells. Thus, Fer is required for maximal p38 kinase activation to promote the chemotaxis of activated mast cells. Further studies with mast cells derived from fps/fes-deficient mice will be required to provide insight into the role of Fps/Fes in mast cell activation.
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PMID:Fer kinase is required for sustained p38 kinase activation and maximal chemotaxis of activated mast cells. 1219 36

Mast cells express the high affinity IgE receptor FcepsilonRI, which upon aggregation by multivalent antigens elicits signals that cause rapid changes within the mast cell and in the surrounding tissue. We previously showed that FcepsilonRI aggregation caused a rapid increase in phosphorylation of both Fer and Fps/Fes kinases in bone marrow-derived mast cells. In this study, we report that FcepsilonRI aggregation leads to increased Fer/Fps kinase activities and that Fer phosphorylation downstream of FcepsilonRI is independent of Syk, Fyn, and Gab2 but requires Lyn. Activated Fer/Fps readily phosphorylate the C terminus of platelet-endothelial cell adhesion molecule 1 (Pecam-1) on immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and a non-ITIM residue (Tyr(700)) in vitro and in transfected cells. Mast cells devoid of Fer/Fps kinase activities display a reduction in FcepsilonRI aggregation-induced tyrosine phosphorylation of Pecam-1, with no defects in recruitment of Shp1/Shp2 phosphatases observed. Lyn-deficient mast cells display a dramatic reduction in Pecam-1 phosphorylation at Tyr(685) and a complete loss of Shp2 recruitment, suggesting a role as an initiator kinase for Pecam-1. Consistent with previous studies of Pecam-1-deficient mast cells, we observe an exaggerated degranulation response in mast cells lacking Fer/Fps kinases at low antigen dosages. Thus, Lyn and Fer/Fps kinases cooperate to phosphorylate Pecam-1 and activate Shp1/Shp2 phosphatases that function in part to limit mast cell activation.
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PMID:Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation. 1673 27

KIT receptor is required for mast cell development, survival, and migration toward its ligand stem cell factor (SCF). Many solid tumors express SCF and this leads to mast cell recruitment to tumors and release of mediators linked to tumor angiogenesis, growth, and metastasis. Here, we investigate whether FES protein-tyrosine kinase, a downstream effector of KIT signaling in mast cells, is required for migration of mast cells toward SCF-expressing mammary tumors. Using a novel agarose drop assay for chemotaxis of bone marrow-derived mast cells (BMMC) toward SCF, we found that defects in chemotaxis of fes-null BMMCs correlated with disorganized microtubule networks in polarized cells. FES displayed partial colocalization with microtubules in polarized BMMCs and has at least two direct microtubule binding sites within its N-terminal F-BAR and SH2 domains. An oligomerization-disrupting mutation within the Fer/CIP4 homology-Bin/Amphiphysin/Rvs (F-BAR) domain had no effect on microtubule binding, whereas microtubule binding to the SH2 domain was dependent on the phosphotyrosine-binding pocket. FES involvement in mast cell recruitment to tumors was tested using the AC2M2 mouse mammary carcinoma model. These tumor cells expressed SCF and promoted BMMC recruitment in a KIT- and FES-dependent manner. Engraftment of AC2M2 orthotopic and subcutaneous tumors in control or fes-null mice, revealed a key role for FES in recruitment of mast cells to the tumor periphery. This may contribute to the reduced tumor growth and metastases observed in fes-null mice compared with control mice. Taken together, FES is a potential therapeutic target to limit the progression of tumors with stromal mast cell involvement.
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PMID:FES kinase promotes mast cell recruitment to mammary tumors via the stem cell factor/KIT receptor signaling axis. 2258 10