998 resultados para Miller, William, 1782-1849
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Using both confocal immunofluorescence microscopy and biochemical approaches, we have examined the role of β-arrestins in the activation and targeting of extracellular signal-regulated kinase 2 (ERK2) following stimulation of angiotensin II type 1a receptors (AT1aR). In HEK-293 cells expressing hemagglutinin-tagged AT1aR, angiotensin stimulation triggered β-arrestin-2 binding to the receptor and internalization of AT1aR-β-arrestin complexes. Using red fluorescent protein-tagged ERK2 to track the subcellular distribution of ERK2, we found that angiotensin treatment caused the redistribution of activated ERK2 into endosomal vesicles that also contained AT1aR-β-arrestin complexes. This targeting of ERK2 reflects the formation of multiprotein complexes containing AT1aR, β-arrestin-2, and the component kinases of the ERK cascade, cRaf-1, MEK1, and ERK2. Myc-tagged cRaf-1, MEK1, and green fluorescent protein-tagged ERK2 coprecipitated with Flag-tagged β-arrestin-2 from transfected COS-7 cells. Coprecipitation of cRaf-1 with β-arrestin-2 was independent of MEK1 and ERK2, whereas the coprecipitation of MEK1 and ERK2 with β-arrestin-2 was significantly enhanced in the presence of overexpressed cRaf-1, suggesting that binding of cRaf-1 to β-arrestin facilitates the assembly of a cRaf-1, MEK1, ERK2 complex. The phosphorylation of ERK2 in β-arrestin complexes was markedly enhanced by coexpression of cRaf-1, and this effect is blocked by expression of a catalytically inactive dominant inhibitory mutant of MEK1. Stimulation with angiotensin increased the binding of both cRaf-1 and ERK2 to β-arrestin-2, and the association of β-arrestin-2, cRaf-1, and ERK2 with AT1aR. These data suggest that β-arrestins function both as scaffolds to enhance cRaf-1 and MEK-dependent activation of ERK2, and as targeting proteins that direct activated ERK to specific subcellular locations.
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Editors: Oct. 1807-June 1812, George Manners.--July 1812-Aug. 1814, William Jerdan.
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"Edition limited to 200 copies."
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Cover title: Pauper abstract for 1848.
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"Edition Peters, No. 3002."
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Mode of access: Internet.
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"List of continental authors cited": p. [xi]-xvi; "American authorities": p. [xvii]-xviii.
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Mode of access: Internet.
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Vol. 5: Indexes and maps.
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Appendix A: The traditional policy of Russia (from "Russia and England", 1880) vol. II, p. 457-470; Appendix B: A nation's protest against war (from the "Northern echo" of January 17, 1878) vol. II, p. 471-475.
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Includes bibliographical references.
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Mode of access: Internet.
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Mode of access: Internet.
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Mode of access: Internet.
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Title on spine: Professor Smyth's lectures on modern history.