955 resultados para Lennox, William Pitt, Lord, 1799-1881.


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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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The Raf-1 protein kinase is a major activator of the ERK MAPK pathway, which links signaling by a variety of cell surface receptors to the regulation of cell proliferation, survival, differentiation and migration. Signaling by Raf-1 is regulated by a complex and poorly understood interplay between phosphorylation events and protein-protein interactions. One important mode of Raf-1 regulation involves the phosphorylation-dependent binding of 14-3-3 proteins. Here, we have examined the mechanism whereby the C-terminal 14-3-3 binding site of Raf-1, S621, controls the activation of MEK-ERK signaling. We show that phosphorylation of S621 turns over rapidly and is enriched in the activated pool of endogenous Raf-1. The phosphorylation on this site can be mediated by Raf-1 itself but also by other kinase(s). Mutations that prevent the binding of 14-3-3 proteins to S621 render Raf-1 inactive by specifically disrupting its capacity to bind to ATP, and not by gross conformational alteration as indicated by intact MEK binding. Phosphorylation of S621 correlates with the inhibition of Raf-1 catalytic activity in vitro, but 14-3-3 proteins can completely reverse this inhibition. Our findings suggest that 14-3-3 proteins function as critical cofactors in Raf-1 activation, which induce and maintain the protein in a state that is competent for both ATP binding and MEK phosphorylation.

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Resumen: Descripción: retrato de 3/4 de William Pultney sentado y de perfil

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This letter was sent to Tudor's brother in Paris, France, via a Mr. Bromfield.

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One octavo-sized leaf containing a handwritten letter from William Winthrop to Professor Pearson scheduling a meeting between the Committee of the town of Cambridge and Harvard administrators.

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Two folio-sized leaves containing a one-and-a-half-page handwritten letter from Winthrop to Bentley discussing James Dallaway's Constantinople, Ancient and Modern, and Greek mythology.

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This letter written to his father describes his arrival at Harvard, book expenses, and present financial situation; he also asks his father to build him a writing desk. Willard discusses the family of his uncle, Harvard president Joseph Willard, and his uncle’s health and issues with jaundice.

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Willard details his various expenses for food, wood, tuition, and books, and explains his bill payment schedule. He also mentions President Willard and sends best wishes to his mother, brother, and sister.