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)

The reactive sulfhydryls of human adult and fetal hemoglobin and the single sulfhydryl of isolated gamma chains have been spin labeled with N-(1-oxyl-2,2,5,5-tetramethyl-3-pyrrolidinyl) iodoacetamide. Similar electron paramagnetic spectral differences between oxy- and deoxy-modified hemoglobins were observed for both these hemoglobins and for the isolated chains, indicating that ligand-induced conformational changes occur in isolated hemoglobin subunits as well as intact hemoglobin tetramers. Ligand induced changes in the reactivity of p-hydroxymercuribenzoate with the sulfhydryl groups of both intact hemoglobins and isolated subunits, observed by McDonald and Noble (1974) J. Biol. Chem. 249, 3161-3165), led them to draw a similar conclusion. Following carboxypeptidase A digestion of these modified hemoglobins and gamma chains, a procedure which specifically removes the two C-terminal residues of the beta or gamma chains, spectral differences between the liganded and unliganded spin-labeled derivatives still persisted. However, the magnitude of this difference was not only more reduced in the case of the hemoglobins than in that of the subunits but the spectra of both the oxy and deoxy derivatives of the hemoglobins were characteristic of the oxy derivative of a cooperative tetrameric hemoglobin. These findings support the premise that the COOH-terminal end of the beta or gamma chain contributes, although possibly to different extents, to the spectral differences exhibited by both the spin-labeled hemoglobins and chains.
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PMID:Ligand-induced conformational changes in spin label-modified human hemoglobins and chains and their carboxypeptidase A-digested derivatives. 18 24

Natural killer cells express an Fc receptor for IgG (CD16) in association with disulfide-linked dimers composed of two homologous subunits: the zeta chain of the T cell antigen receptor complex and the gamma chain of the mast cell/basophil Fc receptor for IgE. The ability of zeta and gamma to transduce CD16-mediated activation signals was compared by reconstituting distinct CD16 receptor isoforms composed of various combinations of zeta- and gamma-containing dimers. Stably transformed non-hematopoietic and hematopoietic cell lines were established that expressed chimeric molecules comprising the extracellular domain of CD16 joined to the transmembrane and intracellular domains of zeta or gamma. Reconstituted CD16 receptor complexes triggered Ca2+ influx, tyrosine phosphorylation, and IL-2 production in stable transformants of the Jurkat T cell line. However, cross-linking of the CD16/gamma chimera induced a specific pattern of tyrosine phosphorylation and was more efficient at signal transduction than a CD16, zeta-zeta complex, suggesting that zeta and gamma cytoplasmic domains may be coupled to distinct tyrosine kinase pathways that differentially regulate CD16-mediated activation signals. By contrast, both CD16/zeta and CD16/gamma chimeric molecules were not functional in stable transformants of the fibroblast Chinese Hamster Ovary cell line, indicating a requirement for downstream signaling components present in hematopoietic cells. Finally, the zeta transmembrane domain appears to preferentially associate with CD16 rather than the CD3:TCR complex, suggesting that a hierarchy of molecular interactions governs NK and T cell differentiation.
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PMID:Signaling function of reconstituted CD16: zeta: gamma receptor complex isoforms. 147 81

Monoclonal DNP-specific IgG (lambda 2 epsilon 2), IgM (kappa 2 mu2) and IgG [kappa 2 (gamma 1)2] were isolated fom the culture supernatant of hybridomas by affinity chromatography with 2,4-dinitrophenol bovine serum albumin (DNP-BSA) sepharose and characterized by biochemical and biological methods. The molecular weights were 84,200 for the epsilon chain, 55,400 for the gamma chain and 77,500 for the mu chain as determined by sodium dodecylsulphate polyacrylamide del electrophoresis (SDS-PAGE). The association constants for [3H]-DNP-lysine determined by equilibrium dialysis were 0 . 87 X 10(7) l/mol for IgE and 1 . 91 X 10(8) 1/mol for IgG1. The isoelectric focusing of the purified monoclonal antibodies revealed for IgG1 seven bands at a pH range of 6 . 3 - 7 . 2 and for IgE sixteen bands at a pH range of 4 . 5 to 6 . 8. the binding of 125I-anti-IgE to rat basophilic leukaemia (RBL) and rat mast cells which had been preincubated with various amounts of monoclonal IgE was studied. At saturation conditions of IgE, about 2 . 14 X 10(5) molecules of anti-IgE were bound per rat mast cell. Rat mast cells coated with monoclonal anti-DNP IgE were triggered for the release of histamine in the presence of either the antigen or guinea-pig anti-mouse IgE. A mutual inhibition of the passive cutaneous anaphylaxis (PCA) reaction in the rat by either mixing mouse reaginic serum directed against ovalbumin or rat reaginic serum directed against Nippostrongylus brasiliensis with monoclonal mouse anti-DNP IgE was demonstrated.
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PMID:Generation of monoclonal murine anti-DNP-IgE, IgM and IgG1 antibodies: biochemical and biological characterization. 618 Sep 75

A population of cells that express mast cell markers, including the membrane protein p161, but that lack expression of the high affinity IgE receptor, Fc epsilon RI, can be routinely grown from bone marrow. Ionomycin, but not IgE immune complexes, causes these cells to release serotonin and to express IL-3 and IL-13 mRNA, consistent with their being FC epsilon RI-deficient mast cells. These p161+/Fc epsilon RI- mast cells expressed normal amounts of Fc epsilon RI alpha and beta chain mRNA, but extremely low levels of Fc epsilon RI gamma chain mRNA. In addition, this novel mast cell population expressed CD3 zeta chain mRNA, which p161+/Fc epsilon RI+ mast cells did not. CD3 zeta stable transfectants of Abelson-murine leukemia virus-transformed p161+/Fc epsilon RI+ mast cells continued to express Fc epsilon RI. This strongly suggests that the failure of p161+/Fc epsilon RI- mast cells to express IgE receptors was not caused by the presence of CD3 zeta chain. Transfection of human Fc epsilon RI gamma cDNA into p161+/Fc epsilon RI- mast cells rescued IgE binding. These stable transfectants released serotonin in response to cross-linkage of Fc epsilon RI, demonstrating that the molecular defect of p161+/Fc epsilon RI- mast cells is indeed the loss of Fc epsilon RI gamma expression.
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PMID:Mast cells lacking the high affinity immunoglobulin E receptor are deficient in Fc epsilon RI gamma messenger RNA. 762 13

Protein-tyrosine phosphorylation plays a critical role in the high-affinity IgE receptor (Fc epsilon RI) signaling. Here we investigated the involvement of the tyrosine kinase p72syk in Fc epsilon RI signaling in the rat mast cell line RBL-2H3. Specific antibodies were raised against peptides synthesized on the basis of the deduced peptide sequence of an essentially full-length rat syk cDNA. The expression of p72syk in RBL-2H3 cells was demonstrated with these antibodies. The aggregation of Fc epsilon RI led to the tyrosine phosphorylation of p72syk that was detected after 15 s of stimulation, reached a plateau by 5 min, and was not induced by calcium influx or protein kinase C activation. Association of p72syk with the tyrosine phosphorylated Fc epsilon RI gamma chain was detected only after receptor aggregation. We previously demonstrated that aggregation of the Fc epsilon RI on mast cells results in the tyrosine phosphorylation of a 72-kDa protein (pp72) involved in IgE signaling. The depletion of p72syk from RBL-2H3 cell lysates resulted in only a slight decrease in the amount of pp72. These results demonstrate that pp72 is composed of several phosphoproteins and identify p72syk as one component of pp72. These data, together with recent observations in T cells, indicate that the interaction between p72syk-related tyrosine kinases and zeta-related proteins could play an important role in signal transduction.
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PMID:Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation. 769 87

Interleukin-9 (IL-9) is a multifunctional cytokine produced by activated TH2 clones in vitro and during TH2-like T cell responses in vivo. The IL-9 receptor is a member of the hemopoietin receptor superfamily and interacts with the gamma chain of the IL-2 receptor for signal transduction. Various observations indicate that IL-9 is actively involved in mast cell responses by inducing the proliferation and differentiation of these cells. The role of IL-9 in T cell responses is less clear. Although freshly isolated normal T cells do not respond to IL-9, this cytokine induces the proliferation of murine T cell lymphomas in vitro and in vivo overexpression of IL-9 results in the development of thymic lymphomas. In the human, the existence of an IL-9-mediated autocrine loop has been suggested for some malignancies such as Hodgkin's disease. Other potential biological targets for IL-9 include B lymphocytes, hematopoietic progenitors, and immature neuronal cell lines.
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PMID:Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. 788 4

The gamma chain of the high affinity receptor for immunoglobulin E is a member of the T-cell antigen receptor zeta chain family and a functional subunit common to both T-cell and Fc receptors. Here we report that the gamma chain is phosphorylated on threonine in response to protein kinase C activation. Furthermore, the threonine phosphorylation of the gamma chain correlates with the endocytosis of this receptor. We identified a receptor-associated kinase as the calcium-independent protein kinase C-delta and found that it associates with the carboxyl-terminal cytoplasmic domain of the beta chain. In addition, protein kinase C-delta was the only isozyme capable of phosphorylating the gamma chain in vitro. These findings provide evidence for the functional role of protein kinase C-delta in early signal transduction events in the mast cell and suggest a more general mechanism of activation for receptors that share subunits of the zeta chain family.
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PMID:Phosphorylation of the gamma chain of the high affinity receptor for immunoglobulin E by receptor-associated protein kinase C-delta. 808 12

The gamma subunit of immunoglobulin Fc receptors is an essential component of the high-affinity receptor for IgG (Fc gamma RIII) and is associated with the high-affinity receptor for IgG (Fc gamma RI) and the T cell receptor-CD3 complex. It is required for both receptor assembly and signal transduction. Targeted disruption of this subunit results in immunocompromised mice. Activated macrophages from gamma chain-deficient mice unexpectedly lack the ability to phagocytose antibody-coated particles, despite normal binding. Defects in NK cell-mediated antibody-dependent cytotoxicity and mast cell-mediated allergic responses are evident in these animals, establishing the indispensable role of FcRs in these responses. However, loss of gamma chain does not appear to perturb T cell development, since both thymic and peripheral T cell populations appear normal. These mice thus represent an important tool for evaluating the role of these receptors in humoral and cellular immune responses.
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PMID:FcR gamma chain deletion results in pleiotrophic effector cell defects. 831 72

Aggregation of the high affinity receptor for IgE (FcepsilonRI) on the mucosal mast cell line, RBL-2H3, results in the rapid and persistent tyrosine phosphorylation of Vav. Immunoprecipitation of Vav from activated cells revealed co-immunoprecipitated phosphoproteins of molecular weights identical to the FcepsilonRI beta and gamma chains, and the former was reactive with antibody to the FcepsilonRI beta chain. Conversely, Western blots revealed the presence of p95 Vav in FcepsilonRI immunoprecipitates. The association of Vav and of Grb2 with the receptor was found to be regulated by aggregation of the receptor, and the interaction of Vav with the FcepsilonRI was localized to the gamma chain. To gain insight on the signaling pathway in which Vav participates, we investigated the in vivo associations of Vav with other molecules. A reducible chemical cross-linking agent was used to covalently maintain protein interactions under nonreducing conditions. A fraction of Vav increased in mass to form a complex of >300 kDa in molecular mass. Under reducing conditions the cross-linked Vav immunoprecipitates showed the presence of Grb2, Raf-1, and p42(mapk) (ERK2). In vitro kinase assays of Raf-1 activity associated with Vav revealed that this complex had an activity greater than that of Raf-1 derived from nonactivated cells, and aggregation of the FcepsilonRI did not modulate this activity. In contrast, aggregation of the FcepsilonRI increased the total Raf-1 activity by 2-5-fold. These results demonstrate that Vav associates constitutively with components of the mitogen-activated protein kinase pathway to form an active multimeric signaling complex whose in vivo activity and associations may be directed by aggregation of the FcepsilonRI. The findings of this study may also be relevant to other members of the immune recognition receptor family that share the T-cell antigen receptor zeta/gamma chains.
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PMID:Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex. 890 Jan 82

We attempted to elicit active anaphylaxis to ovalbumin, or passive IgE- or IgG1-dependent anaphylaxis, in mice lacking either the Fc epsilonRI alpha chain or the FcR gamma chain common to Fc epsilonRI and Fc gammaRI/III, or in mice lacking mast cells (KitW/ KitW-v mice), and compared the responses to those in the corresponding wild-type mice. We found that the FcR gamma chain is required for the death, as well as for most of the pathophysiological changes, associated with active anaphylaxis or IgE- or IgG1-dependent passive anaphylaxis. Moreover, some of the physiological changes associated with either active, or IgG1-dependent passive, anaphylactic responses were significantly greater in Fc epsilonRI alpha chain -/- mice than in the corresponding normal mice. Finally, while both KitW/KitW-v and congenic +/+ mice exhibited fatal active anaphylaxis, mast cell-deficient mice exhibited weaker physiological responses than the corresponding wild-type mice in both active and IgG1-dependent passive systemic anaphylaxis. Our findings strongly suggest that while IgE antibodies and Fc epsilonRI may influence the intensity and/or kinetics of some of the pathophysiological changes associated with active anaphylaxis in the mouse, the mortality associated with this response can be mediated largely by IgG1 antibodies and Fc gammaRIII.
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PMID:Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaRIII. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. 906 48


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