Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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

Interleukin 3 (IL-3) is a T cell-derived lymphokine that supports the growth and development of hematopoietic cells. Tyrosine phosphorylation has been suggested to play an important role in IL-3-dependent cell proliferation. To test whether a growth factor receptor carrying a tyrosine kinase can be functional in IL-3 dependent cells, we used a retroviral vector to introduce the human EGF receptor into a murine IL-3-dependent pre-mast cell line, IC2. The EGF receptors expressed on the infected clones bind EGF with both high and low affinities. EGF stimulates the infected cells for a short term growth response. In the presence of IL-3 and EGF, infected clones differentiate into more mature mast cells characterized by increases in intracellular granulation and histamine content. This differentiation is reversible when EGF is removed. EGF induces tyrosine phosphorylation of several cellular proteins and the expression of oncogenes c-fos and c-myc, in a manner analogous to IL-3 stimulation. These results indicate that the EGF receptor is functional in the pre-mast IC2 cells; EGF can support short-term proliferation and activates the signals that induce cell differentiation. Thus, EGF receptor-expressing IC2 cells provide a unique cellular system for in vitro study of mast cell differentiation.
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PMID:EGF induces differentiation of an IL-3-dependent cell line expressing the EGF receptor. 253 Oct 81

The proteolipid of rabbit sarcoplasmic reticulum was isolated and characterized. Tyrosine was identified as the C-terminal amino acid by hydrazinolysis and carboxypeptidase A digestion. The N-terminal sequence of proteolipid is: Met-Glx-Arg-Ser-Thr-Arg-Glx-Leu-Cys-Leu-Asp-Phe. The hydrophilic character of the N-terminal portion suggests that it is exposed on the membrane surface.
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PMID:Purification and characterization of the proteolipid of rabbit sarcoplasmic reticulum. 645 Jun 18

We compare the detailed binding modes of the 39-amino acid inhibitor from potatoes, glycyl-L-tyrosine, the ester analogue CH3OC6H4(CO)CH2CH(CO2(-))C6H5, and indole acetate to the exopeptidase carboxypeptidase A (EC 3.4.17.1). In the potato inhibitor, cleavage of the COOH-terminal glycine-39 leaves a new carboxylate anion of valine-38 having one oxygen on zinc and the other as a receptor of a hydrogen bond from tyrosine-248 of carboxypeptidase. Tyrosine-248 also receives a hydrogen bond from the amide proton of the originally penultimate peptide bond between tyrosine-37 and valine-38. This hydrogen bond suggests product stabilization which is available to peptides and depsipeptides but not to esters lacking an equivalent peptide bond (nonspecific esters). Also, this structure may represent the intermediate binding step for the uncleaved substrate as it moves along the binding subsites. In particular, this may be the binding mode for the substrate after association of the COOH-terminal region of the substrate with the residues at binding subsite S2 (tyrosine-198, phenylalanine-279, and arginine-71) and preceding entry into the catalytic site S1'. These stabilized complexes allow some understanding of the effect of indole acetate, shown here to bind in the pocket at S1', as a competitive inhibitor for esters (for which entry into S1' precedes the rate-determining catalytic step for hydrolysis) and as a noncompetitive inhibitor for peptides (for which entry into S1' is rate limiting). These results, including the binding mode of the ester analogue, are consistent with the original proposal from x-ray studies that both esters and peptides are cleaved with the carboxy terminus at S1', although not necessarily by the same chemical steps.
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PMID:Binding of ligands to the active site of carboxypeptidase A. 694 83

Tyrosine contributions to the structure-function relationship in the fructose-1, 6-biphospate aldolase from C. capitata have been investigated. There are three well defined groups of tyrosine residues with different roles in the structure of the insect aldolase. C-terminal tyrosine residues are essential for the maintenance of the catalytic conformation. Releasing of these residues by carboxypeptidase A treatment results in complex conformational changes according to CD studies. Another tyrosine residue group is located at the active site, and the substrate, fructose-1, 6-biphosphate, protects it upon nitration. Chemical modification of this residue results in enzyme activity changes similar to those induced by carboxypeptidase digestion. Enzyme-substrate interaction results in a change of the microenvironment of at least three tyrosine residues per subunit with different accessibility for tetranitromethane.
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PMID:Role of tyrosine residues on structure-function of fructose-1,6-biphosphate aldolase from Ceratitis capitata. 711 91

Tubulin tyrosine ligase catalyzes the reversible addition of tyrosine to the C-terminus of tubulin alpha chains. By using ligase and carboxypeptidase A in conjunction, we have previously shown that brain cytoplasmic tubulin exists in three forms: 15-40% already has C-terminal tyrosine, another 10-30% can accept additional tyrosine, and about one-half is an uncharacterized species which is not a ligase substrate. A membrane-bound fraction of brain tubulin, purified by vinblastine precipitation from a detergent extract, has been found to differ by the complete absence of preexisting tyrosine. The membrane fraction from which tubulin was extracted also contained masked forms of both ligase and a distinct detyrosylating enzyme, which can be released by detergent extraction. The turnover of alpha-chain C-terminal tyrosine in vivo was studied by incubating brain mince with labeled tyrosine, or injecting it intracerebrally, under conditions where protein synthesis was inhibited. Tyrosine appeared to turn over to about the same extent in membrane-bound, as in soluble, tubulin. This apparently paradoxical result was not due to ATPase in the membrane fraction, which might have allowed ligase-catalyzed exchange between free and fixed tyrosine. Authentic [14C]tyrosylated tubulin added to the brain membrane fraction was not detyrosylated or subject to endoprotease digestion during subsequent procedures to isolate tubulin. The unexpected finding that tubulin tyrosylated at the C-terminal in vivo appears to be in the "non-substrate" fraction points toward a possible resolution of the paradox.
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PMID:An apparent paradox in the occurrence, and the in vivo turnover, of C-terminal tyrosine in membrane-bound tubulin of brain. 745 80

In the present study we examined the activation of Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2) after aggregation of cell-surface high-affinity Fc receptors for IgE (Fc epsilon RI) on mast cells. MCII mast cells (a factor-dependent bone-marrow-derived murine mast cell line) produce significant amounts of leukotriene C4 (LTC4) (70 ng/10(6) cells) on cross-linking of Fc epsilon RI. Using enzymic and immunochemical analysis we found that cPLA2 is the predominant form of this enzyme in MCII mast cells (0.2 micrograms/mg of total protein) and other forms (i.e. secretory PLA2 or Ca2+ independent cytosolic PLA2) could not be detected. Therefore MCII mast cells represent an excellent cellular model for the study of the biochemical mechanism(s) responsible for Fc epsilon RI-induced activation of cPLA2 and the involvement of cPLA2 in Fc epsilon RI-mediated production of LTC4. After activation of Fc epsilon RI by cross-linking, cPLA2 in MCII mast cells exhibited a decreased electrophoretic mobility and its enzyme activity was increased 3-fold. Treatment with phosphatase reversed both the altered electrophoretic mobility and the enhanced enzyme activity demonstrating that they were the result of Fc epsilon RI-induced phosphorylation. On cross-linking of Fc epsilon RI, cPLA2 was phosphorylated within 30 s and appeared to be an early substrate for Fc epsilon RI-activated protein kinases in MCII mast cells. Tyrosine phosphorylation may be a critical component in this process, as genistein, an inhibitor of protein tyrosine kinases, blocked the activation of cPLA2. Using anti-phosphotyrosine antibodies we observed that the activating phosphorylation was not on tyrosine residues of cPLA2, indicating that tyrosine kinases participate upstream in the signalling cascade that couples Fc epsilon RI to cPLA2. We conclude that in MCII mast cells cPLA2 is activated by kinase-dependent mechanisms and may be responsible for Fc epsilon RI-induced mobilization of arachidonic acid for the generation of LTC4.
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PMID:Phosphorylation and activation of Ca(2+)-sensitive cytosolic phospholipase A2 in MCII mast cells mediated by high-affinity Fc receptor for IgE. 781 99

The SH2 domain-containing inositol-polyphosphate 5-phosphatase, SHIP, associates with FcgammaRIIB and negatively regulates both B-cell and mast cell function. We report here that SHIP was tyrosine-phosphorylated after high affinity IgE receptor (FcepsilonRI) aggregation in rat basophilic leukemia RBL-2H3 cells. The tyrosine phosphorylation of SHIP was an early event after receptor aggregation and was present in cells deficient in the protein-tyrosine kinase Syk. Furthermore it was not secondary to the increase of intracellular calcium or the activation of protein kinase C. SHIP was precipitated by immobilized phosphorylated synthetic peptides based on the immunoreceptor tyrosine-based activation motif (ITAM) of the beta but not the gamma subunit of the high affinity IgE receptor. Tyrosine phosphorylation of SHIP and its association with the tyrosine-phosphorylated beta subunit of FcepsilonRI could play an important role in down-regulating receptor-mediated signal transduction in mast cells. Thus, whereas the activation molecule Syk associates with the gamma subunit ITAM, the beta subunit ITAM binds the negative signaling molecule SHIP. Therefore, unlike B cells where the antigen receptor and coreceptors such as FcgammaRIIB or CD22 each recruits molecules with opposite effects, the FcepsilonRI contains subunits which recruit molecules that activate and inhibit signal transduction.
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PMID:The negative signaling molecule SH2 domain-containing inositol-polyphosphate 5-phosphatase (SHIP) binds to the tyrosine-phosphorylated beta subunit of the high affinity IgE receptor. 915 64

Aggregation of the FcepsilonRI, a member of the immune receptor family, induces the activation of proteintyrosine kinases and results in tyrosine phosphorylation of proteins that are involved in downstream signaling pathways. Here we report that Pyk2, another member of the focal adhesion kinase family, was present in the RBL-2H3 mast cell line and was rapidly tyrosine-phosphorylated and activated after FcepsilonRI aggregation. Tyrosine phosphorylation of Pyk2 was also induced by the calcium ionophore A23187, by phorbol myristate acetate, or by stimulation of G-protein-coupled receptors. Adherence of cells to fibronectin dramatically enhanced the induced tyrosine phosphorylation of Pyk2. Although Src family kinases are activated by FcepsilonRI stimulation and tyrosine-phosphorylate the receptor subunits, the activation and tyrosine phosphorylation of Pyk2 were downstream of Syk. In contrast, tyrosine phosphorylation of Pyk2 by stimulation of G-protein-coupled receptors was independent of Syk. Therefore, the FcepsilonRI-induced tyrosine phosphorylation of Pyk2 is downstream of Syk and may play a role in cell secretion.
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PMID:Activation of protein-tyrosine kinase Pyk2 is downstream of Syk in FcepsilonRI signaling. 940 54

Interleukin-9 (IL-9) is a cytokine with pleiotropic effects on mast cell and T cell lines. It exerts its effects through the IL-9R complex consisting of IL-9Ralpha and the common gammac subunit. Here we report functional evidence for receptor heteromerization for efficient signal transduction, and we define minimal requirements in the two receptor subunits for IL-9R function. Tyrosine 336 of the IL-9Ralpha and the membrane-proximal segment of gammac are both crucial for signaling. The activated IL-9R complex employs the Janus kinases JAK1 and JAK3 for subsequent activation of the signal transducer and activator transcription (STAT) factors STAT-1, STAT-3, and STAT-5. This process is independent of Tyk2. We demonstrate further that the activated STAT complexes consist of STAT-1 and STAT-5 homodimers and STAT-1-STAT-3 heterodimers. Finally, we show that IL-9R signaling in a T cell line does not result in detectable mitogen-activated protein kinase activation and leads to unsustained proliferation. Nonetheless, these T cells are efficiently protected from dexamethasone-induced apoptosis. These results further define the molecular architecture of the IL-9R and its specific connections to various biologic responses.
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PMID:Heteromerization of the gammac chain with the interleukin-9 receptor alpha subunit leads to STAT activation and prevention of apoptosis. 953 18


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