Fc receptor-mediated signal transduction: Roles of PI3K, PKC, calcium flux and tyrosine phosphorylation.
Item
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Title
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Fc receptor-mediated signal transduction: Roles of PI3K, PKC, calcium flux and tyrosine phosphorylation.
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Identifier
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AAI9521315
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identifier
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9521315
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Creator
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Shen, Zhenhai.
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Contributor
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Adviser: Jay C. Unkeless
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Date
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1995
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology | Chemistry, Biochemistry
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Abstract
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Receptors for the Fc domain of IgG (Fc{dollar}\gamma{dollar}R) on leukocytes mediate a pleiotropic response following crosslinking by immune complexes. Signaling events following crosslinking of B and T cell antigen receptors, Fc{dollar}\epsilon{dollar}RI, and Fc{dollar}\gamma{dollar}Rs share common elements. In each, signaling is initiated by receptor crosslinking by antigen or immune complexes, and results in the activation of src family kinases and ZAP-70-related tyrosine kinases, which associate with members of the receptor complex. Subsequent events include phosphorylation on tyrosine of multiple cellular substrates, (Ca{dollar}\sp{lcub}2+{rcub}{dollar}) {dollar}\sb{lcub}\rm i{rcub}{dollar} transient and phagocytosis. Shc, Syk, phospholipase C-{dollar}\gamma{dollar}1 are rapidly phosphorylated on tyrosine residues upon crosslinking of human Fc{dollar}\gamma{dollar}RIIA transfected into P388D{dollar}\sb1,{dollar} a murine macrophage cell line. The {dollar}\rm\lbrack Ca\sp{lcub}2+{rcub}\rbrack\sb{lcub}\rm i{rcub}{dollar} transient, activation of PI 3-kinase, as well as protein tyrosine phosphorylation, are necessary for both Fc{dollar}\gamma{dollar}RIIA and Fc{dollar}\gamma{dollar}RIIIB-mediated phagocytosis. Enhanced PI 3-kinase activity is associated with activated PLC-{dollar}\gamma1{dollar} in transfected macrophages. Tyrosine phosphorylation of PLC-{dollar}\gamma1{dollar} is necessary but not sufficient for stimulated activity of the enzyme and release of IP3, its activity is dependent on PI 3-kinase activity. Crosslinking of Fc{dollar}\gamma{dollar}RIIA in macrophages results in activation of PKC-{dollar}\delta.{dollar} Protein kinase C activation in neutrophils serves to blunt phagocytosis, particularly following Fc{dollar}\gamma{dollar}RIIIB activation, perhaps by inhibiting Ca{dollar}\sp{lcub}2+{rcub}{dollar} flux.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
