993 resultados para Clark, William H., 1835-1864.


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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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Letter to William Dickson from Thomas Clark regarding Mr. Goring’s claims and Clark Street’s affair with Brackbill (1 ¼ pages, handwritten), June 15, 1821.

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Letter to the Honourable William Dickson from Thomas Clark. Mr. Clark says that he would have been off a week ago if not for the Robert Hamilton arbitration. There is a hole in this letter and a slight bit of the text is affected (3 ½ pages, handwritten), April 14, 1829.

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Indenture between William Dickson and Thomas Clark (as per the Last Will and Testament of Robert Hamilton) of Niagara to Joseph Gatehill of Grimsby for the Lot lettered G in the Town of Grimsby. The document is torn and slightly stained. This does not affect the text, Aug. 19, 1819.

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Indenture (vellum) of bargain and sale between William Dickson, Thomas Dickson and Thomas Clark, executors of the late Robert Hamilton of Queenston to George Moffat for land in Burford, Beverly and Grimsby, Ontario, Feb. 27, 1827.

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Indenture between the Honourable William Dickson of Galt and John Clark of Dumphries for 100 acres in the Township of Dumphries in the County of Halton, June 17, 1830.

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Bond (1 page, printed) between Isaac Sterling of the Township of Salt fleet to William Dickson of Niagara and Thomas Clark of Queenston (regarding the Last Will and Testament of Robert Hamilton) for payment of 153 pounds, 12 shillings and 3 pence to be made to Dickson and Clark, May 21, 1819.

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Bond (1 page, printed) between Archibald Johnston of the Township of Bertie to William Dickson of Niagara and Thomas Clark of Queenston (regarding the Last Will and Testament of Robert Hamilton) for payment of 75 pounds to be made to Dickson and Clark, June 7, 1821.

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Bond (1 page, printed) between Daniel Cornell of the County of Oxford to William Dickson of Niagara and Thomas Clark of Stamford (regarding the Last Will and Testament of Robert Hamilton) for payment of 103 pounds, 11 shillings and 1 penny to be made to Dickson and Clark, July 12, 1822.

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This essay examines aspects of the serialisation of the novels of William Clark Russell, the greatest late Victorian nautical novelist. Focusing on the treatment of his work by the Edinburgh firm of Messrs Chambers, the article provides an illuminating perspective on market censorship in this period. Drawing on the archives of Chatto & Windus and the literary agent A.P. Watt, it traces the network of relations between author, agent, magazine editor and book publisher, showing how the various components of the serial market operated in the late 1880s and early 1890s.