SUMMARY
The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY) signaling pathways. Genome-wide screening of human SH2 domains reveals that ≈90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction is important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, these studies reveal how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY signaling pathways.
A new zirconium precursor, (ZrCl 2 [N(SiMe 3 ) 2 ] 2 ), and H 2 O oxidant were used to deposit ZrO 2 films on a Si substrate, for alternative gate dielectrics, via atomic layer deposition (ALD) in the temperature range 150±350 C. The film growth showed the self-limiting characteristic of ALD, with a maximum growth rate of 1.6 per cycle at 175 C. The compositions of as-deposited films were analyzed by Rutherford backscattering spectroscopy (RBS), X-ray photoelectron spectroscopy (XPS), and secondary ion mass spectroscopy (SIMS), and it was found that the amount of silicon in ZrO 2 films was uniformly distributed throughout the film in the range of 1.1 at.-% to 5.4 at.-% as the deposition temperature was increased. After rapid thermal annealing in an Ar atmosphere at 700±900 C, the amorphous as-deposited film was crystallized mainly in the cubic phase, and no significant change in surface morphology was observed.
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