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Receptor protein-tyrosine kinases, through phosphorylation of specific tyrosine residues, generate high-affinity binding sites which direct assembly of multienzyme signalling complexes. Many of these signalling proteins, including phospholipase C gamma, GTPase-activating protein and phosphatidylinositol-3-OH kinase, contain src-homology 2 (SH2) domains, which bind with high affinity and specificity to tyrosine-phosphorylated sequences. The critical role played by SH2 domains in signalling has been highlighted by recent studies showing that mutation of specific phosphorylation sites on the platelet-derived growth factor receptor impair its association with phosphatidylinositol-3-OH kinase, preventing growth factor-induced mitogenesis. Here we report the solution structure of an isolated SH2 domain from the 85K regulatory subunit of phosphatidylinositol-3-OH kinase, determined using multidimensional nuclear magnetic resonance spectroscopy. The structure is characterized by a central region of beta-sheet flanked by two alpha-helices, with a highly flexible loop close to functionally important residues previously identified by site-directed mutagenesis.  相似文献   
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Booker JR  Favetto A  Pomposiello MC 《Nature》2004,429(6990):399-403
Beneath much of the Andes, oceanic lithosphere descends eastward into the mantle at an angle of about 30 degrees (ref. 1). A partially molten region is thought to form in a wedge between this descending slab and the overlying continental lithosphere as volatiles given off by the slab lower the melting temperature of mantle material. This wedge is the ultimate source for magma erupted at the active volcanoes that characterize the Andean margin. But between 28 degrees and 33 degrees S the subducted Nazca plate appears to be anomalously buoyant, as it levels out at about 100 km depth and extends nearly horizontally under the continent. Above this 'flat slab', volcanic activity in the main Andean Cordillera terminated about 9 million years ago as the flattening slab presumably squeezed out the mantle wedge. But it is unknown where slab volatiles go once this happens, and why the flat slab finally rolls over to descend steeply into the mantle 600 km further eastward. Here we present results from a magnetotelluric profile in central Argentina, from which we infer enhanced electrical conductivity along the eastern side of the plunging slab, indicative of the presence of partial melt. This conductivity structure may imply that partial melting occurs to at least 250 km and perhaps to more than 400 km depth, or that melt is supplied from the 410 km discontinuity, consistent with the transition-zone 'water-filter' model of Bercovici and Karato.  相似文献   
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Elimination of 5 mu particles from the human lung   总被引:7,自引:0,他引:7  
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It is generally believed that animals make decisions about the selection of mates, kin or food on the basis of pre-constructed recognition templates. These templates can be innate or acquired through experience. An example of an acquired template is the feeding preference exhibited by larvae of the moth, Manduca sexta. Naive hatchlings will feed and grow successfully on many different plants or artificial diets, but once they have fed on a natural host they become specialist feeders. Here we show that the induced feeding preference of M. sexta involves the formation of a template to a steroidal glycoside, indioside D, that is present in solanaceous foliage. This compound is both necessary and sufficient to maintain the induced feeding preference. The induction of host plant specificity is at least partly due to a tuning of taste receptors to indioside D. The taste receptors of larvae fed on host plants show an enhanced response to indioside D as compared with other plant compounds tested.  相似文献   
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The Cenozoic collision between the Indian and Asian continents formed the Tibetan plateau, beginning about 70 million years ago. Since this time, at least 1,400 km of convergence has been accommodated by a combination of underthrusting of Indian and Asian lithosphere, crustal shortening, horizontal extrusion and lithospheric delamination. Rocks exposed in the Himalaya show evidence of crustal melting and are thought to have been exhumed by rapid erosion and climatically forced crustal flow. Magnetotelluric data can be used to image subsurface electrical resistivity, a parameter sensitive to the presence of interconnected fluids in the host rock matrix, even at low volume fractions. Here we present magnetotelluric data from the Tibetan-Himalayan orogen from 77 degrees E to 92 degrees E, which show that low resistivity, interpreted as a partially molten layer, is present along at least 1,000 km of the southern margin of the Tibetan plateau. The inferred low viscosity of this layer is consistent with the development of climatically forced crustal flow in Southern Tibet.  相似文献   
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